Novel 2-substituted-3,4-epoxycyclopentan-1-ones, 2-substituted-3,4-epoxycyclopentan-1-ols, and various 2-substituted-cyclo-pentenones

ABSTRACT

This disclosure describes 2-substituted-3,4-epoxycyclopentan-1-ones, 2-substituted-3,4-epoxycyclopentan-1-ols, and various 2-substituted-cyclopentenones useful as intermediates for the preparation of certain 11-hydroxy- and 11-deoxy-9-keto(or hydroxy)-prostenoic acid derivatives which possess bronchodilator, hypotensive, and anti-ulcer activity.

This is a division of application Ser. No. 737,941 filed Nov. 2, 1976,which is in turn a divisional of application Ser. No. 603,467, filedAug. 11, 1975, which is in turn a divisional of application Ser. No.355,101, filed Apr. 27, 1973, all now abandoned.

BRIEF SUMMARY OF THE INVENTION

This invention relates to novel hydroxy substituted prostanoic acids andderivatives as well as to intermediates and methods for theirpreparation. These methods embrace novel and useful procedures for thepreparation of prostaglandin E₁, 11-deoxyprostaglandin E₁,13-dihydroxyprostaglandin E₁, and other known biologically importantprostaglandin congeners. The novel compounds of this invention may berepresented by the following general formula: ##STR1## wherein n is aninteger having the value 1 or 2; R₁ is hydrogen, lower alkoxy,triphenylmethyl, or triphanylmethyl in which one or two of the phenylrings is substituted with an alkyl or an alkoxy group having up to 3carbon atoms; R₂ is a straight chain alkyl group having from 2 to 10carbon atoms, a straight chain alkyl group having from 2 to 10 carbonatoms and substituted with one or two alkyl groups each having from oneto three carbon atoms, a straight chain alkonyl group having from 3 to10 carbon atoms, a straight chain alkenyl group having from 3 to 10carbon atoms and substituted with one or two alkyl groups having betweenthem from 8 to 5 carbon atoms, or a straight chain alkenyl group havingfrom 3 to 10 carbon atoms; P is hydroxy or an alkoxy group having from 1to 10 carbon atoms; Y is a divalent radical selected from the groupconsisting of those of the formulae: ##STR2## Z is a divalent radicalselected from the group consisting of those of the formulae: ##STR3##wherein m is an integer from 3 to 8, inclusive, p is an integer from 2to 6 inclusive, R₄ is an alkyl group having up to 3 carbon atoms, and R₅is an alkyl group having up to 3 carbon atoms, a fluorine atom, or aphenyl group; R₆ is hydrogen or an alkyl group having up to three carbonatoms; R₇ is a hydrogen or an alkyl group having up to 3 carbon atoms;and the moiety-C₁₂ -C₁₄ - is ethylene, trans-vinylene, or cis-vinylene;with the first proviso that when n is 1, R₁ is hydrogen, R₇ is hydrogen,Z is -(CH₂)₁₃ - and -C₁₃ -C₁₄ - is ethylene or trans-vinylene then R₂does not include a straight chain alkyl group having from 2 to 10 carbonatoms; and with the second proviso that when Z is ##STR4## R₁ ishydrogen, R₂ is a straight chain alkyl group having from 2 to 10 carbonatoms and R₇ is hydrogen then -C₁₃ -C₁₄ - is ethylene or cis-vinylene;and with the third proviso that when R₄ is alkyl then R₁ is hydrogen;and with the fourth proviso that only one unsaturated bond can bedirectly adjacent to C₁₃ ; and with the fifth proviso that when R₇ is analkyl group then the groups attached to the C₈ position may have the8α-alkyl(8-iso) configuration of the formula: ##STR5##

Embraced within the scope of the present invention are all the possibleoptical isomers of the above general formula. Also embraced within thescope of the present invention are the non-toxic, pharmaceuticallyacceptable salts of the novel compounds of the present invention when R₃is hydroxy. The cations comprised in these salts include, for example,the non-toxic metal cations such as the sodium ion, potassium ion,calcium ion, and magnesium ion as well as the organic amine cations suchas the tri(lower alkyl)amine cations (e.g., triethylamine,triethanolamine) procaine, and the like.

The novel compounds of the present invention are usually obtainable asoils having characteristic absorption spectre. They are relativelyinsoluble in water but are relatively soluble in common organic solventssuch as ethanol, ethyl acetate, dimethylformamide, and the like. Thecationic salts of the compounds when R₃ is hydroxy are, in general,white to yellow crystalline solids having characteristic melting pointsand absorption spectre. They are relatively soluble in water, methanol,and ethanol but are relatively insoluble in benzene, diethyl ether, andpetroleum ether.

DETAILED DESCRIPTION OF THE INVENTION

The prostaglandins are a family of closely related compounds which havebeen obtained from various animal tissues, and which stimulate smoothmuscle, lower arterial blood pressure, antagonize epinophrine-inducedmobilization of free fatty acids, and have other pharmacological andautopharmacological effects in mammals. See Bergstrom et al., J. Biol.Chem. 238, 3555 (1963) and Horton, Experientia 21, 113 (1965) andreferences cited therein. All of the so called natural prostaglandinsare derivatives of prostanoic acid: ##STR6## The hydrogen atoms attachedto C-8 and C-12 are in trans-configuration. When the two side-chains (orthe C-8 and C-12 hydrogens) are cis to each other, the compounds arereferred to as 8-iso prostaglandins. The natural prostaglandinsrepresent only one of the possible optical isomers. The compounds ofthis invention include all possible optical isomers.

The novel compounds of the present invention may be readily preparedfrom certain cycloalkenone intermediates which may be represented by thefollowing general formula: ##STR7## wherein R'_(s) is an alkoxy grouphaving from 1 to 12 carbon atoms; and n and z are as hereinabovedefined.

The cycloalkenone intermediates may be readily prepared from2-carbethoxycyclopentanone or 2-carbethoxycyclohexanone in accordancewith the reaction schemes set forth in Flowsheets A, B, C, I and J.##STR8## wherein m and n are as hereinabove defined and X is iodo orbromo. In accordance with this reaction scheme, the cycloalk-2-en-1-ones(VIII) are developed by first converting 2-carbethoxycyclopentanone or2-carbethoxycyclohexanone (I) to the sodium enolates thereof by means ofsodium hydride in dimethoxyethane and then treating the sodium esolatewith an ethyl ω-haloalkanoate (II). There is thus obtained thecorresponding 2-carbethoxy-2-(ω-carbethoxyalkyl)cycloalkanone (III)which is then hydrolyzed and decarboxylated to afford the2-(ω-carboxyalkyl)cycloalkanone (IV). This acid is then esterified withethanol whereby the 2-(ω-carbethoxyalkyl)cycloalkanone (V) is obtained.The reaction conditions for carrying out the above sequence of reactionsare well known in the art. The conversion of the cycloalkanone (V) tothe enol acetate (VI) is effected by heating with acetic anhydride inthe presence of p-toluenesulfonic acid. Preparation of the enol acetate(VI) usually requires heating for a period of from about eight tothirty-six hours. During this period, it is preferable to allowby-product acetic acid to distill out in order to force the reaction tocompletion. The bromination of the enol acetates (VI) to the2-bromocycloalkanones (VII) is preferably carried out in a two phasesystem as follows. A solution of bromine in chloroform is added to arapidly stirred mixture of a solution of the enol acetate (VI) inchloroform and an aqueous solution of an acid acceptor such as calciumcarbonate or soda ash. This addition is carried out at 0° -5° C. over aperiod of about half an hour, stirring is continued for an additionalperiod of about half an hour to a few hours, and the product (VII) isthen isolated by standard procedures. The dehydrobromination of the2-bromocycloalkanones (VII) is preferably carried out indimethylformamide with a mixture of lithium bromide and lithiumcarbonate at the reflux temperature for a period of about 30 minutes toan hour or so. The so formed cycloalk-2-en-1-ones (VIII) are alsoisolated by standard procedures well known in the art. Substitution ofX--(CH₂)_(m) --C(R₄)₂ --CH₂ --CO₂ C₂ H₃ for (II) in Flowsheet A andcarrying through the sequence of transformations illustrated therein isproductive of the following cycloalk-2-on-1-one (VIIIa): ##STR9##wherein X, n, m and R₄ are as hereinabove defined.

The required cycloalk-2-en-1-one intermediates of general structure(XVI), wherein the side-chain has a lower alkyl group, fluorine atom orphenyl group alpha to the carbethoxy function, may be prepared inaccordance with the following reaction scheme: ##STR10## wherein n, mand R₆ are as hereinabove defined and G is a lower alkyl or aryl group.In accordance with this reaction scheme, the2-(ω-carbethoxyalkyl)cycloalk-2-en-1-ones (IX) are converted to thecorresponding 1-methoximino-2-(ω-carbethoxyalkyl)-2-cycloalkenes (X) bytreatment with methoxyamine. With the ring carbonyl function thusblocked it is possible to effect a preferential reduction of the estergroup by treatment with diisobutylaluminum hydride. The resultingalcohol (XI) is converted to a tosylate derivative (XII), whichundergoes displacement on treatment with the sodium salt of a diethylR_(s) -substituted malonate (XIII) to provide the disubstituted malonatederivatives (XIV). Hydrolysis and decarboxylation as well asconcomittant cleavage of the methoximino blocking group provides thedesired 2-(ω-carboxy-ω-R_(s) -substituted-alkyl)cycloalk-2-en-1-ones(XV), which are readily converted to the corresponding ester (XVI) bythe usual procedure via the acid chloride and subsequent treatment withthe appropriate alcohol in the presence of a tertiary amine.

The requisite 2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-ones (XXII)and 2-(ω-carbethoxy-ω-1-thia-alkyl)-cycloalk-2-en-1-ones (XXVI) may beprepared in accordance with the reaction schemes of Flowsheet C, whereinn and m are as hereinbefore defined. ##STR11## In accordance with thereaction scheme shown in Flowsheet C, for the preparation of the oxaderivative (XXII), an appropriate2-(ω-carbethoxyalkyl)cycloalk-2-en-1-one (XVII) is converted to thecorresponding methoxime (XVIII), the ester function of which is thenpreferentially reduced with diisobutylaluminum hydride to afford themethoxime alcohol (XIX). The alcohol (XIX) is converted on treatmentwith n-butyl lithium to the lithio alcoholate, which then is O-alkylatedby reaction with ethyl bromoacetate to provide (XX). Hydrolysis withacetone-aqueous hydrochloric acid furnishes the deblocked keto-acid(XXI), which is then re-esterified with ethanol in the presence ofp-toluenesulfonic acid to give the required2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-one (XXII). O-Alkylationcan also be accomplished by treatment of the lithio alcoholate of (XIX)with sodium or other metal salt of bromoacetic acid, in which case thefree carboxylic acid corresponding to ester (XX) is obtained. Hydrolysisas for (XX) provides the keto acid (XXI).

The preparation of the thia derivative (XXVI), proceeds from theintermediate alcohol (XIX), which after conversion to the tosylateintermediate (XXIII) and reaction with the sodium salt of ethylmercaptoacetate furnishes intermediate (XXIV). Deblocking of XXIV) withacetone-aqueous hydrochloric acid provided the keto-acid (XXV), which onre-esterification with ethanol gives the required2-(ωcarbethoxy-ω-1-thia-alkyl)cycloalk-2-en-1-ones (XXVI).

Certain of the 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivativesof this invention, as defined in the general formula on page 1 above,may be prepared from the cycloalkenone (XXXI) and the triphenylmethoxysubstituted 1-alkyne (XXVII) as depicted in Flowsheet D. In Flowsheet D,n, R_(s), R's and Z are as hereinabove defined; R's is a straight chainalkyl group having from 2 to 10 carbon atoms, a straight chain alkylgroup having from 2 to 10 carbon atoms and substituted with one or twoalkyl groups having from one to three carbon atoms, a straight chainalkenyl methyl group having from two to nine carbon atoms, or a straightchain alkenyl methyl group having from two to nine carbon atoms andsubstituted with one or two alkyl groups having between them 2 to 5carbon atoms; and R is a lower alkyl group. ##STR12##

In accordance with the reaction scheme of Flowsheet D, thetriphenylmethoxy substituted 1-alkyne (XXVII) is treated withdiisobutylaluminum hydride (XXVIII). This reaction of the 1-alkyne(XXVII) with diisobutylaluminum hydride (XXVIII) provides the alane(XXIX) containing the trans-double bond and is carried out in an inertsolvent such as benzene, toluene, and the like at temperatures in therange of 40°-60° C. for several hours. It can also be carried out in asolvent such as tetrahydrofuran, usually in an appropriate 2:1 mixturewith benzene or hexane; in which case the reaction requires somewhatmore vigorous conditions, usually treating at about 70°-75° C. for abouteighteen hours. The subsequent reaction with methyl or n-butyl lithium(R-Li) is preferably carried out in a mixture of the above solvents withan ether-type solvent such as diethyl ether, dibutyl ether,tetrahydrofuran and the like. This reaction is rapid and is preferablycarried out at 0°-10° C. with cooling. The conjugate 1,4-addition of theresulting alanate salt (XXX) to the cycloalk-2-en-1-one (XXXI) ispreferably carried out at ambient temperatures for a period of 12 to 24hours. This reaction is also best carried out in an ether-type solventsuch as diethyl ether, dibutyl ether, tetrahydrofuran, and the like. Theintermediate alanate-enolate adduct is then carefully hydrolyzed in situwith dilute hydrochloric acid with cooling, and the products (XXXII) areisolated in the usual manner well known in the art. Removal of thetriphenylmethyl blocking group can then be accomplished by treating withweak acid. A preferred procedure involves heating at 45° C. for 3.5hours in a solvent system consisting of aceticacid:tetrahydrofuran:water in the proportion of 4:2:1. Saponification inthe usual manner of the resulting alkyl ester (XXXIII, R_(s) -alkoxy)provides the corresponding carboxylic acid (XXXIII, R_(s) -OH).

All available evidence leads us to the conclusion that in the product(XXXIII) the two side-chains attached to C₈ and C₁₂ are trans to eachother. However, we are not certain of the configurational relationshipin product (XXXII) as it is obtained directly from the alanate process.These products may have the side-chains in a trans or cis relationshipor they may be a mixture containing both the trans- and cis-isomers.This is indicated in the nomenclature of the compounds involved by thedesignation of 8ξ. In order to ensure a trans-relationship in both(XXXII) and (XXXIII) these products can be submitted to conditions knownin the literature to equilibrate the cis-8-iso-PGE₁ to a mixturecontaining about 90% of the trans product. These conditions involvetreatment with potassium acetate in aqueous methanol for 96 hours atroom temperature.

The triphenylmethyl blocking group for the hydroxy function in (XXVII)etc. is an important feature of this process and other oxygen blockinggroups, e.g., tetrahydropyranyl and alkyl, are not compatible with aclean cis-addition of diisobutyl aluminum hydride (XXVIII) to the alkyne(XXVII) to provide the desired trans-vinyl function. Alternativeprocedures for the preparation of novel lithio alanate reagents usefulfor the introduction of the Δ¹³ -trans 15-oxy β-chain by conjugate1,4-addition are illustrated in Flowsheet K further below.

The intermediates for the introduction of the Δ¹³ - 15-hydroxyside-chain are an integral part of this invention and they may berepresented by the following general formulae (A), (B), (C), (D) and (E)wherein R's is as hereinabove defined, R is a lower alkyl group, notnecessarily the same for each use, and R' is an alkyl group having fromone to ten carbon atoms not necessarily the same for each use, W₁ islower alkoxy, triphenylmethyl, or a triphenylmethyl group in which oneor two of the phenyl rings is substituted with a lower alkoxy group; W₂is lower alkoxy, triphenylmethyl, a triphenylmethyl group in which oneor two of the phenyl rings is substituted with a lower alkoxy group,tetrahydropyranyl, α-(lower alkoxy) substituted lower alkyl, t-butyl, ora tri-(lower alkyl)silyl group; X₁ is iodo or bromo; s is an integerhaving the value of one to three inclusive, and t is an integer havingthe value of one to three inclusive, with the proviso that the sum of sand t must be equal to four. ##STR13## The alanate conjugate additionprocedure is also useful for the synthesis of prostaglandin E₁ (XL) asillustrated in Flowsheet E. This reaction sequence is carried out in thesame manner as described for the sequence in Flowsheet D. It is to benoted that the introduction of the Δ¹³ - 15-oxy chain proceeds trans tothe 11-oxy function. For this synthesis, it is best to use thetetrahydropyranyl or trialkylsilyl esters, since these esters can behydrolyzed under contitions compatible with the stability of the β-ketolfeature of prostaglandin E₁ . Alkyl esters would be hydrolyzed byfermentation with Baker's Yeast. The tetrahydropyranyl or trialkylsilyl,and triphenylmethoxy blocking groups are removed by mild acid treatment,for example with acetic acid:tetrahydrofuran:water (4:2:1) as describedhereinabove. Application of the lithio alanate conjugate additionprocess to the synthesis of prostaglandins E₂ and E₃ is described belowin connection with Flowsheet N.

The 13-dihydro derivatives (C₁₃ C₁₄ is ethylene) of this invention canbe prepared by reduction of the Δ¹³ function in the corresponding13-prostenoic acids or esters. This reduction can be accomplished byhydrogenation. However this procedure is not cleanly applicable in thepresence of other double bonds in the molecule. In the latter instancethe 13-dihydro derivatives are preparable via conjugate addition of aGrignard derivative (XLII) to cycloalkenone (XLI) in the presence of acatalyst such as the tributylphosphine cuprous iodide complex as setforth in Flowsheet F, wherein, n, Z, R₂ and R's are as hereinabovedefined; Q is a blocking group; and X is chlorine, bromine or iodine,preferably bromine or iodine. The blocking group (Q) for the hydroxylfunction in (XLII) can be any group stable to the Grignard reagent andwhich can later be removed by chemical treatment (e.g., mild hydrolysisor catalytic hydrogenolysis in the absence of carbon to carbon doublebonds elsewhere in the molecule) to which the remainder of the moleculeis stable. Suitable blocking groups, therefore, may be, for example,benzyl, diphenylmethyl, triphenylmethyl, tetrahydropyranyl, or a moietyof the formula: ##STR14## wherein R₁₁ is hydrogen, methyl or ethyl.Among the above-described blocking groups, we have found tert-butyl tobe particularly convenient and useful. ##STR15##

In accordance with the above reaction scheme, the conjugate 1,4-additionof a 3-(substituted hydroxy)alkyl or alkenyl magnesium halide (XLII) toa cycloalk-2-en-1-one (XLI) is carried out in the presence of acatalyst. In general, Grignard reactions with conjugated ketones provide1,2-addition products; conjugate 1,4-addition is usually accomplishedwhen the reaction is carried out in the presence of a cuprous chlorideor cuprous acetate catalyst. It is therefore most unexpected that thereaction of the cycloalkenone (XLI) with a Grignard reagent (XLII) inthe presence of either of the aforementioned catalysts does not giveappreciable amounts of the desired 1,4-conjugate addition products. Thenovel feature of our process is provided by the use, as a catalyst, of acuprous halide complex with a trisubstituted phosphine, a trialkylphoshonate, a tertiary amine or a heterocycle containing a basicnitrogen (e.g., pyridine). We have found it preferable to usetributylphosphine-cuprous iodide complex; (C₄ H₉)₃ P·CuI. The reactionis best carried out in the usual way in an ether-type solvent such asdiethyl ether, dibutyl ether, tetrahydrofuran, and the like, at roomtemperature for a period of time of from two to eighteen hours. Theintermediate magnesium halide-enolate adduct is then hydrolized in situ,preferably with ammonium chloride, at room temperature and the product(XLIII) is isolated in the usual manner well known in the art.

When the blocking group is a tertiary alkyl moiety such as tert-butyl,deblocking of (XLIII) to afford (XLIV) is conveniently effected bytreatment with glacial trifluoroacetic acid at from -5° C. to 10° C. fora period of one to three hours. Since this procedure may lead to partialtrifluoroacetylation of the free hydroxy function, it is preferablyfollowed by treatment with aqueous ammonia (about 1.0M concentration)for about 15 minutes at ambient temperatures. When the blocking group istetrahydropyranyl, its removal is readily effected with dilute acid.When the blocking group is a moiety such as benzyl, diphenylmethyl ortriphenylmethyl, deblocking of (XLIII) is convenientyl effected bycatalytic hydrogenolysis, procedures for which are well known in theart. In the instance of triphenylmethyl, deblocking is preferablyeffected by treating with acetic acid:tetrahydrofuran:water (4:2:1) atabout 45° C. for about 3.5 hours.

Mild acid treatment results in hydrolysis of the tetrahydropyranylesters; alkyl esters can be hydrolyzed by the usual saponificationtechniques.

When the cycloalkanone esters (XLIII) are formed by quenching of thereaction mixture with aqueous ammonium chloride solution, the relativestereochemical relationship of the two side-chains is not known withcertainty. Therefore, the bond linking the Grignard-derived side-chainto the cycloalkyl ring is indicated by a bond in (XLIII). However, inany case, the subsequent deblocking and ester hydrolysis proceduresensure the development, at least in predominant proportion, of thethermodynamically favored trans-relationship between the twoside-chains, as is depicted in structure (XLIV) of the reaction scheme.

An alternative method for the introduction of the Δ¹³⁻ 15-hydroxyside-chain involves 1,4-conjugate addition to cycloalkenone (LV) of avinyl Grignard reagent [(LIII)+(LIV)] in the presence of a catalyst suchas the tributylphosphine cuprous iodide complex followed by deblocking.From this process, in addition, to the product (LVIII) containing theC₁₃ -C₁₄ moiety as a trans-vinylene function there also is obtained thecorresponding product (LIX) in which the C₁₃ -C₁₄ moiety is acic-vinylene function. These novel cis-Δ¹³ derivatives are also embracedwithin the scope of this invention. The reaction sequence for the"vinyl" Grignard process is illustrated in flowsheet G, which follows,and in which W₂, n, Z, R_(s) and R'₃ are as hereinabove defined, and R"₂is a straight chain alkyl group having from 2 to 10 carbon atoms, or astraight chain alkyl group having from 2 to 10 carbon atoms andsubstituted with one or two alkyl groups having from one to three carbonatoms. ##STR16##

In accord with the reaction sequence of Flowsheet G the vinyl Grignardreagent (LIII+LIV), is prepared under an inert atmosphere in arelatively limited amount of anhydrous tetrahydrofuran. More vigorousconditions (e.g., heating in an oil bath at 70°-80° C., one hour), forthe formation of the Grignard reagent (LIII+LIV) favors the proportionof Δ¹³ -cis isomer (LIX) in the product of conjugate addition. Wilderconditions (for example 35°-47° C., one hour) favors the proportion ofΔ¹³ -trans isomer (LVIII) in the final product.

Conjugate addition of the vinyl Grignard reagent mixture [(LIII)+(LIV)]to cycloalkenone (LV) is then preferably carried out by addition of theGrignard to the cycloalkenone dissolved in an ether type solvent, e.g.,diethylether, containing a catalyst such as thetributylphosphine-cuprous iodide complex at a temperature of about 0° C.After a period of about thirty minutes to three hours the reactionmixture is poured onto aqueous concentrated ammonium chloride solutionto give (LVI)+(LVII). As explained hereinabove, at this stage therelationship of the two side-chains to each other is not determined. Inany event, deblocking the 15-hydroxy function with weak acid (whichprocedure also hydrolyzes trialkylsilyl or tetrahydropyranyl esters)provides the product (LVIII) and (LIX) in which the chains are trans toeach other. In the instance of alkyl esters, saponification provides thecorresponding carboxylic acids. The Δ¹³ -cis and Δ¹³ -trans-isomers canbe separated from each other by the usual techniques of chromatography;particularly useful is liquid-liquid partition chromatography.

The precursor 3-hydroxy-1-trans-alkenyl bromides (LI) can be prepared,as illustrated in Flowsheet G, by condensation of acetylene (XLV) withan acid chloride (XLVI) in the presence of aluminum trichloride. Theresulting 3-oxo-1-chloro-trans-1-alkylene (XLVII) is then converted tothe corresponding 1-bromo derivative (XLVIII), by reaction with excesslithium bromide. This reaction is preferably carried out in ketonesolvents, such as 2-pentanone or acetone. Reduction of the 3-ketofunction in (XLVIII), with for example, sodium borohydride provides thealcohol (LI). The alcohol function is then blocked to give (LII).Alternatively, the 3-oxo vinyl bromide (XLVIII) can be prepared directlyfrom the acyl bromide (L) and acetylene (XLIX) in the presence ofaluminum tribromide, preferably in ethylene dibromide.

The "vinyl Grignard" procedure outlined in Flowsheet G represents anovel, useful and convenient procedure for the synthesis of13-prostenoic acids and the novel Grignard reagents represented byformulae (LIII) and (LIV) are to be considered as embraced within thescope of this invention.

The "vinyl Grignard" technique can also be applied to a useful synthesisof prostaglandin E₁ and the novel Δ¹³ -cis-prostaglandin-E₁ asillustrated in Flowsheet H, below. Thus, treatment of cyclopentanone(LX) with Grignard [(LXI)+(LXII)] in accordance with the considerationsdiscussed hereinabove, provides the conjugate addition products (LXIII)plus (LXIV), mild acid hydrolysis of which furnishes prostaglandin E₁(LXV) and Δ¹³ -cis prostaglandin E₁ (LXVI), separable by chromatography.##STR17##

The preparation of the cycloalkenone intermediates (LXXVI, LXXVII)bearing a cis double bond in the carboxylic acid side chain can beaccomplished by the sequence illustrated in Flowsheet I, which followsand in which n and p are as hereinabove defined. ##STR18##

In the above Flowsheet I, the sequence wherein a2-carbalkoxycycloalkanone (LXVII) is transformed to a2-(β-hydroxyethyl)cycloalk-2-en-1-one (LXXIII) is carried out in themanner described in Flowsheet A. Methyl ether cleavage of thecorresponding 2-(β-methoxymethyl)cycloalkenone is achieved by treatingwith boron tribromide. Oxidation of the alcohol (LXXIII) with Collinareagent [chromium trioxide-pyridine complex in methylene chloride underanhydrous conditions; J. C. Collins, W. W. Hess, and F. J. Frank,Tetrahedron Letters, 3363 (1968)] provides the aldehyde (LXXIV), whichis then treated in anhydrous dimethylsulfoxide with the ylid (LXXV)prepared from an (ω-carboxyalkyl)triphenyl phosphonium bromide andsodium hydride. The use of dimethylsulfoxide as a solvent for thisreaction leads to the predominant formation of the desired cis doublebond derivative (LXXVI). The acid function in (LXXVI) can be esterifiedin the usual fashion; with diazomethane, the methyl ester (LXXVII) isobtained.

Cyclopentanones such as (LXXVI wherein n-1) may also be prepared by thesequence illustrated in Flowsheet J, which follows and in which p is ashereinabove defined. ##STR19##

In Flowsheet J above the bicyclic hemiacetal (LXXVIII) [P. A. Grieco,Journ. Org. Chem., 37, 2363 (1972)] is treated with ylid (LXXIX) to givethe 1-hydroxy-3-cyclopentene (LXXX). Oxidation with Jones reagent givesthe corresponding ketone (LXXXI), which on base treatment furnishes therequired cyclopentenone (LXXXII), which can then be esterified in theusual manner.

Certain of the intermediates illustrated in Flowsheets I and J, inparticular the compounds of formulae (LXXI), (LXXII), (LXXIII), (LXXIV),(LXXVI) (LXXVII) (and related esters), (LXXX) and (LXXXI) are novel anduseful compounds and are embraced within the scope of this invention.

Alternative procedures for the preparation of the alanate intermediatesto that discussed in connection with Flowsheet D above are illustratedbelow in Flowsheet K, wherein R', R'₂, R"₂ and W₂ are as hereinabovedefined. ##STR20##

In accordance with the sequence of Flowsheet K above the1-iodo-trans-1-alkenyl-3-oxo derivative (LXXXIV) is prepared by iodideinterchange, preferably in acetone or similar ketone, from thecorresponding chloride (LXXXIII), the preparation of which is describedin connection with Flowsheet G above. Reduction of (LXXXIV) to thealcohol (LXXXVI) can be accomplished in the usual manner with sodiumborohydride. The hydroxy function is then blocked to give (LXXXV, R'₂-R"₂). Treatment of the acetylene, ##STR21## with one equivalent ofdisiamylborane (prepared in situ from diborane and 2-methyl-2-butene)and then with excess anhydrous trimethylamine oxide followed bytreatment with an aqueous solution of excess sodium hydroxide and atetrahydrofuran solution of excess iodine is also productive of (LXXXV).Treatment of the trans-1-alkenyl iodide (LXXXV) at low temperatures,preferably at about -30° C. to -78° C., in an inert solvent, e.g.,hexane or toluene, with an alkyl lithium, e.g., butyl lithium, providesthe trans-1-alkenyl lithium reagent (LXXXVII). Treatment of this lithioderivative with a tri-alkyl aluminum furnishes the trans-1-alkenyltrialkyl alanate (LXXXVIII). Treatment of a dialkyl aluminum chloridewith two molar equivalents of lithio reagent (LXXXVII) gives thebis(trans-1-alkenyl)dialkyl alanate (LXXXIX) and treatment of analkylaluminum dichloride with three molar equivalents of lithio reagent(LXXXVII) affords the tris(trans-1-alkenyl)alkyl alanate (XC).

Each of the three types of alanates, (LXXXVIII), (LXXXIX) and (XC), canbe utilized for 1,4-conjugate addition reactions as describedhereinabove in connection with Flowsheets D and E above. Thus,substitution of (LXXXVIII), (LXXXIX) or (XC) for alanate (XXX) inFlowsheet D will provide the indicated products of the Flowsheet.Similarly, substitution of (LXXXVIII), (LXXXIX) or (XC) in which R'₂ isn-pentyl for alanate (XXXVII) in Flowsheet E provides prostaglandins E₁.In general the mono alkenyl alanate (LXXXVII) is preferred because it ismore economical in the use of vinyl halide.

With regard to the cycloalkenones of Flowsheets D, E, F, G and H itshould be noted that the blocking groups for the 4-hydroxy function aswell as for the carboxylic acid may also be a tri-alkylsilyl group,e.g., trimethylsilyl, dimethyl-t-butylsilyl or dimethylisopropylsilyl.Cyclopentenones blocked in this manner are illustrated below in formula(XCI) and (XCII) wherein m, n, Z and R' (not necessarily the same foreach use) are as hereinabove defined. ##STR22##

All the novel products of this invention exclusive of certainintermediates bear a hydroxy or any function substituted at or at whatultimately becomes the C₁₅ atom of the product prostanoic acids andesters. Thus in at lest most insances a 15-"normal" and a 15-"epi"racemate is obtained in at least near equal proportions. Each of theracemates contains equal amounts of the enantiomer wherein C₁₅ is in theS configuration and the enantiomer wherein it is in the R configuration.The racemates are separable from each other by the usual techniques ofchromatography. Also, resolution in the usual way of the β-chainprecursor [for example, the resolution of 3-hydroxy-1-octyne isdescribed in the literature; [see R. Pappo, P. Collins and C. Jung. Ann.N.Y. Acad. of Science, 180 (Prostaglandins), 64(1971); J. Fried et al.,ibid, p. 381]. Resolution prior to the conjugate addition operation willprovide the diastereomers wherein the C₁₅ atom is either in the 15(S) or15(R) configuration, as desired. Separation of the diastereomers soobtained, for example, by chromatography, will give the fully resolved(d and l) products provided there are no asymmetric carbon atoms otherthan at C₈ and C₁₂. The presence of other asymmetric sites requiresadditional resolution steps in order to obtain a single atipode. Thecompounds of this invention embrace all possible optical isomers.

The 11-deoxy-9-keto derivatives (XCIV) of this invention can beconverted to the corresponding 9-hydroxy derivatives. If this conversionis effected with sodium borohydride, the product is a mixture of 9α- and9β-hydroxy derivatives (XCIII) and (XCV) as set forth in the followingreaction scheme: ##STR23## wherein R₂, R₃, R₆, R₇, Z, n and --C₁₃ --C₁₄-- are as hereinabove defined. In general, when the reaction is carriedout with lithium perhydro-9β-boraphenalyl hydride [H. C. Brown and W. C.Dickason, Journ. Amer. Chem. Soc., 92, 709 (1970)] the product is atleast predominantly the 9α-hydroxy derivative (XCIII), wherein the9-hydroxy group is cis to side-chain attached to C₈.

In accordance with accepted convention, an α-substituent at the 8-, 9-,or 12-positions is behind the plane of the paper whereas a β-substituentat these positions is in front of the plane of the paper. This isusually represented by a--bond for an α-substituent, a--bond for aβ-substituent, and a bond where both are indicated. Thus, the 9-hydroxyderivatives may be variously represented as follows: ##STR24##

A useful procedure for the introduction of the 15-lower alkyl group (R₆)is illustrated by the sequences of Flowsheet M, which follows. ##STR25##

In Flowsheet M above n, Z, R₂, R₇ and R₈ are as hereinabove defined. Inthe sequence depicted in Flowsheet M the 9,15-diol (XCVI) is treatedwith 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) (XCVII), whichpreferentially oxidizes the allylic alcohol function at C₁₅ to give the15-ketone (XCVIII). Blocking of the remaining hydroxy function as atrimethylsilyl ether gives (IC) which is reacted with the alkylGrignard, R₂ MgI, to give the 15-alkyl-15-hydroxy derivative (CI).Hydrolysis of the silyl ether blocking group then gives the diol ester(C), saponification of which gives (CII). Oxidation of the secondary9-hydroxy function in (C) provides the 15-alkyl-9-oxo ester (CIII),saponification of which furnishes (CIV). (A similar sequence can beeffected with the Δ¹³ -cis-series.)

The processes of this invention are also useful for the preparation ofprostaglandin E₂ and protaglandin E₃ and thus also PGF₂α and PFG₃α byreduction, for example with lithium perhydro-9b-boraphenalyl hydride.The 4-hydroxycyclopentenone intermediate (CII) required for thesesyntheses is prepared in accordance with the procedure illustrated inFlowsheet N which follows and in which is also shown the transformationof this compound to prostaglandine E₂ and E₃. In Flowsheet N, J is anappropriate blocking group for the hydroxy and ester function in (CII)which is compatible with the conjugate addition reaction and also isultimately removable by acid-catalyzed hydrolysis or other techniqueswhich will not disrupt the sensitive 11-oxy-9-keto system in theproducts (CXIII), (CXV), (CXVIII) and (CXVIX). Particularly useful forthis purpose are the tetrahydropyranyl group and various trialkylsilylgroups (e.g., dimethylisopropylsilyl, trimethylsilyl,dimethyl-t-butylsilyl and the like. ##STR26##

In accordance with the above reaction scheme the 3,4-epoxylactol (CV)[E. J. Corey and R. Moyori, Tetrahedron Letters, 311 (1970)] is treatedwith the ylide (CVI) to give the 3,4-epoxycyclopentanol (CVII) bearingthe α-chain of the prostaglandin 2 series. Oxidation (for example withH₂ CrO₄ -H₂ SO₄ -ether or Jones reagent) of (CVII) provides the epoxyketone (CVIII), mild base treatment of which results in the initialformation of the 4-hydroxycyclopent-2-en1-one (CXI) and the isomeric3-hydroxycyclopent-4-en-1-one (CX) as a mixture. Further treatment ofthis mixture with dilute base under mild conditions (preferably pH10.3-10.6 for 24 hours) results in the isomerization of the 3-hydroxyisomer (CX) to the desired (CXI). We believe that the transformation ofthe epoxy ketone (CVIII) to the hydroxycyclopentenones (CX) and (CXI)and the isomerization of (CX) to (CXI) may take place through theintermediacy of the 3,4-diol (CIX). It is also conceivable thatisomerization of (CX) to (CXI) procedes via the epoxy derivative (CVIII)or the corresponding α-epoxide (CXIb); it is further conceivable that(CVIII) procedes to (CX) and (CXI) directly without the intermediacy of(CIX). Another possible intermediate for the isomerization of (CX) to(CXI) is the corresponding diene (CXIa). The preparation of (CXI) isalso possible via the α-epoxide series from (CXIc) via the α-epoxidecorresponding to (CVII) and (CVIII) such as (CXIb) or via a mixture ofthe α and β epoxides. In practice, it is most convenient to utilize amixture of α- and β-epoxides (CXIc and CV). The hydroxy and acidfunction in the 4-hydroxycyclopentenones (CXI) and then appropriatelyblocked to give (CXII). Appropriate blocking groups aretetrahydropyranyl, trimethylsilyl, dimethyl-isopropylsilyl,dimethyl-t-butylsilyl and the like. Treatment of (CXII) with the lithioalanate (CXIV) or its equivalent (see the discussion hereinabove forFlowsheet K and E) gives the conjugate addition product (CXIII) in whichthe configuration at C₈ is undetermined. Mild acid treatment, forexample with acetic acid:tetrahydrofuran-water,(4:2:1), of (CXIII)results in the removal of blocking groups, and if necessaryequilibration to the all-trans configuration, to give prostaglandinE_(a) (CXV). Similarly treatment of (CXII) with the lithio alanate(CXVI) gives prostaglandin E₆ (CXVII).

Substitution in Flowsheet N, of ylide (CXIX), wherein p is ashereinabove defined, for the ylide (CVI) provides, by transformationsanalogous to those described in Flowsheet N [(CV) to (CXI) and (CXII),the 4-hydroxycyclopent-2-en-1-ones (CXX) and their blocked ether-esters(CXXI). These novel and useful intermediates are a part of the presentinvention. ##STR27##

the 8β-lower alkyl group (R'₇) is introduced as illustrated in FlowsheetO below via the bromomagnesium enolate (CXXV). This novel and usefulintermediate is obtained by conjugate addition of the 1-alkenyl Grignardreagent [(CXXIII) + (CXXIV)], preferably prepared at about 35° C., tothe cycloalkenone (CXXII) in the presence of a catalyst such as thetri-n-butylphosphine cuprous iodide complex as described hereinabove inconnection with Flowsheets G and H. It is also possible to utilize forthese purposes in an analogous manner the magnesio enolate (CXXVII)obtained by conjugate addition of Grignard (XLII) to cycloalkenone (XLI)as described hereinabove in connection with Flowsheet F, in which casethe 13,14-dihydro derivative of this invention are obtained. InFlowsheet O below, n, Z, R₃, R'₃, R'₂, W₂, R₂, Q and X are ashereinabove defined and R'₇ is an alkyl group having up to 3 carbonatoms. When the magnesio enolate (CXXV) is treated with a lower alkylhalide, e.g., methyl iodide, it undergoes alkylation at the 8β-siteproviding, after deblocking of the 15-oxy group in intermediate (CXXVI),the 8β-alkyl derivative (CXXVII). In the instance of alkyl esters,saponification gives the corresponding carboxylic acids (CXXVII, R₃=OH). The compounds corresponding to (CXXVII) wherein C₁₃ -C₁₆ is acis-vinylene double bond are preferably prepared by utilizing the vinylGrignard reagent prepared at temperatures in the range of 70-75° C., asdiscussed hereinabove (Flowsheets G and H).

Also obtained from the alkylationof (CXXV) is the 8α-alkyl-8-isoderivative corresponding to (CXXVI), which after deblocking provides the8α-alkyl-8-iso-products (CXXIX). Usually the 8α-product is formed to asignificantly lesser extent than the 8β-product (CXXVI). The 8α and 8βproducts are separable from each other by the usual technique ofchromatography. ##STR28##

Application of the 8-alkylation process to the 11-oxy series providesthe novel compounds of formula (CXXX), wherein R₁, R₂, R₆, Y and C₁₃-C₁₄ are as hereinabove defined and wherein R'₇ is an alkyl group havingup to 3 carbon atoms, R₈ is selected from the group consisting ofhydrogen, lower alkanoyl, tetrahydropyranyl and tri-lower alkylsilylgroups, R₉ is selected from the group consisting of hydroxy, alkoxyhaving from 1 to 12 carbon atoms, tetrahydropyranyloxy and tri-loweralkyl silyloxy groups, Z₂ is a divalent radical selected from the groupconsisting of those of the formulae- ##STR29## wherein m, p. R₄ and R₅are as hereinabove defined; and the moiety ##STR30## with the provisothat only one unsaturated bond can be directly adjacent to C₁₅ ; andwith the second proviso that when R₄ is alkyl then R₁ is hydrogen; andwith the third proviso that the groups attached to C₈ may be in the8β-alkyl (8-iso) configuration: ##STR31##

The novel compounds of formula (CXXX) are also embraced by thisinvention. The preparation of these compounds may be illustrated by thereaction sequence of Flowsheet P below, wherein R₉, Za, Wa, R"a, R'₇ andR₉ are as hereinabove defined and R'₈ has all the possibilities definedabove for R'₈ except that it is not hydrogen. ##STR32##

In accordance with the sequence of Flowsheet P above, treatment of theether-ester 4-oxycyclopentenone (CXXXI) with the 1-alkylene Grignardreagents [(CXXIII) + (CXXIV)] (see Flowsheet O) gives the bromomagnesioenolate (CXXXII). This operation also results in the introduction of thetrans C₁₃ -C₁₄ double bond (as shown in CXXXII), as well as thecorresponding compound with the cis-double bond. The trans bond isfavored when the Grignard is prepared at lower temperatures, about 35°C.; the cis-bond at higher temperatures, about 70-75° C. This point ismore fully discussed above in connection with Flowsheets G and H. Themagnesio enolate (CXXXII) is a key intermediate and when it is treatedwith a lower alkyl halide, e.g. methyliodide, it undergoes alkylation togive the 8β-lower alkyl derivative (CXXXIII). Deblocking of the15-hydroxy blocking group (e.g., triphenylmethyl), and of the 11-hydroxytetrahydropyranyl or trialkylsilyl ether blocking groups as well as ofthe tetrahydropyranyl or trialkyl silyl esters is accomplished undermild acid conditions, e.g. heating at 45° C. for 3.5 hours in a solventsystem consisting of acetic acid:tetrahydrofuran:meter (4:2:1). Thisprocedure provides (CXXXV). The compounds of structure (CXXXV) or(CXXXIII) can be converted to 8β-alkyl prostaglandins of the A class(CXXXIV) by treatment with acid or base, a preferred procedure involvestreatment in tetrahydrofuran-water (2:1) solvent 0.5N in hydrochloricacid for about seventy hours at ambient temperatures.

The novel compounds of this invention represented by formula (CXXIV) andrelated compounds are particularly interesting since they represent"stabilized" prostaglandin A types, which cannot rearrange to thebiologically relatively inactive prostaglandins of the B series.

Utilization of Grignard (XLII) (see Flowsheet F, hereinabove) in thesequence of Flowsheet P provides the compounds of (CXXX) wherein C₁₃-C₁₄ is ethylene. Provided there are no other double bonds in themolecule these substances can also be obtained by catalytichydrogenation of the compounds represented by formula (CXXXV).

The alkylation process described above for Flowsheets O and P also givesthe corresponding 8α-alkyl derivatives which are separable from the8β-alkyl isomer by chromatography. Thus, for example, in Flowsheet Otreatment of enolate (CXXV) with R'₇ I gives not only the 8β-alkylproduct (CXXVI) as shown, but there also is obtained the 8β-alkylderivative (CXXXVI) shown below. In Flowsheet P, alkylation of enolate(CXXXIX) also provides, in addition to (CXXXXIX) shown, the8α-alkyl-8-iso product (CXXXVII), shown below. These 8α-alkyl-8-isoderivatives can be deblocked and carried through the same series oftransformation shown for the 8β-derivatives (CXXVI) and (CXXXIII) inFlowsheets O and P, respectively. These novel 8β-alkyl-8-iso derivativesand their transformation products are also a part of this invention, asare the key intermediate enolates represented by structures (CXXV) and(CXXXII). ##STR33##

The novel compounds of the present invention have potential utility ashypotensive agents, anti-ulcer agents, agents for the treatment ofgastric hypersecretion and gastric erosion, bronchodilators,antimicrobial agents, anticonvulsants, abortifacients, agents for theinduction of labor, agents for the induction of menses,fertility-controlling agents, central nervous system regulatory agents,analgesic agents, salt and water-rentention regulatory agents,diuretics, fat metabolic regulatory agents, serum-cholesterol loweringagents, anti-inflammatory agents and as agents for the inhibition ofplatelet aggregation, and for the treatment of periodontal disease,glaucoma, uveitis, sickle cell anemia and psorissis. Certain of thenovel compounds of this invention possess utility as intermediates forthe preparation of other of the novel compounds of this invention.

The compounds of this invention provide protection against theulcerogenic properties of indomethacin. This assay was carried out inthe following manner.

Rats were starved for 48 hours (water was given ad libitum).Indomethacin (20 mg./kg. of body weight) was administered by thesubcutaneous route and one-half the dose of the test compound wasadministered by gavage at the same time. After three hours, the secondhalf of the test compound was administered also by Gavage. Five hoursafter the administration of indomethacin the animals were decapitatedand the stomachs removed. The stomachs were washed with distilled water,blotted on gauze, cut along the larger curvature, and the contentsrinsed with distilled water. The stomachs were spread out, pinned on acork and visualized under magnifying glass for ulcers. The criteria forscoring of ulcers was as previously reported. [Abdal-Galil et al. Brit.J. Pharmac. Chomotherapy 33:1-14 (1968)].

Score

0 -- Normal stomach

1 -- Petechial hemorrhage or pin point ulcer

2 -- 1 or 2 small ulcers

3 --Many ulcers, a few large

4 -- Many ulcers, mainly large

Control animals treated with indomethacin but not test compoundconsistently give scores of about 3.0-3.5. Control animals treated withneither indomethacin nor test compound give scores of about 0.5-0.8. Theresults obtained in this assay with typical compounds of the presentinvention are set forth in Table I below. Compounds producing a score of2.5 or lower are considered to be active.

                  TABLE I                                                         ______________________________________                                                 Total Oral                                                                    dose; mg./kg.                                                                 of body   Score                                                      Compound   weight      Treated    Control                                     ______________________________________                                        9-oxo-15-hydroxy-                                                             16-ethyl-13-trans-                                                            prostenoic acid                                                                          25          1.7        3.2                                         9-oxo-15-hydroxy-                                                             13-cis-prostenoic                                                             acid       100         1.3        3.0                                         9-oxo-15-hydroxy-                                                             2-ethyl-15-trans-                                                             prostenoic acid                                                                          50          2.2        3.0                                         9-oxo-8β-methyl-                                                         15-hydroxy-13-                                                                trans-prostenoic                                                              acid       12.5        2.0        3.0                                         9-oxo-3-thia-15-                                                              hydroxy-13-trans-                                                             prostenoic acid                                                                          25          1.8        3.2                                         9-oxo-3-thia-15-                                                              epi-hydroxy-13-                                                               trans-prostenoic                                                              acid       25          2.3        3.2                                         ______________________________________                                    

The novel compounds of the present invention are also effectiveinhibitors of gastric acid secretion and of ulcer development inexperimental animals, and then are potentially valuable as agents forthe control of gastric acid secretion and of gastric erosion and asanti-ulcer agents. Castric acid secretion inhibitory action is usuallymeasured by the "Shay rat" procedure .sup.(1.2) with some modificationsas follows.

The rats (male, CFE strain) were starved for 48 hours (water was givenad libitum) to permit evacuation of stomach contents. On the morning ofthe experiment, under ether anesthesia, the abdominal region was shavedand a midline incision (1-1 1/2") was made with a scapel. With the helpof a closed curved hemostate the duodenum was picked up. Upon gettingthe duodenum into view, fingers were used to pull the stomach throughthe opening, the stomach was then gently manipulated with fingers to ridthe stomach of air and residual matter which were pushed through thepylorus. Two-5 inch sutures were drawn under the pyloric-duodenalpuncture. A ligature, at the juncture was formed with one of thethreads. The second ligature was also formed but not tightened.

The test compound or the vehicle, usually 1 ml./mg. body weight, wereinjected into the duodenum as close as possible to the first ligature.After injection the second ligature was tightened below the injectionsite to minimise leakage. The stomach was placed back through theopening into the abdominal cavity, the area of incision and washed withsaline and the incision was closed with antaclips. (Occasionally,instead of an intraduodenal injection, animals were dosed by the oral orsubcutaneous route. In the latter case, dosing was done thirty to sixtyminutes before the operation).

Three hours later, the rats were decapitated and oranguinated, takingcare that blood did not drain into the esophagus. The abdominal cavitywas exposed by cutting with scissors and the esophagus close to thestomach was clamped off with a hemostat, the stomach was removed bycutting above the hemostat (the esophagus was cut) and between the twosutures. Extraneous tissue was removed, the stomach washed with salineand blotted on gauze. A slit was carefully made in the stomach which washeld over a funnel and the contents were collected in a centifuge tube.The stomach was further cut along the outside edge and turned insideout. Two ml. H₂ O were used to wash the stomach contents into therespective centrifuged tube. The combined stomach contents and wash werethen centifuged out for 10 minutes in the International Size 2Centrifuge (setting at 30). The supernatant was collected, volumemeasured and recorded, 2 drops of a phenolphthalein indicator (1% in 95%ethanol) were added and the solution was titrated with 0.02N NaOH (orwith 0.04 N NaOH large volumes of stomach contents were encountered) topH 8.4 (because of usual coloring of the stomach contents,phenolphthalein was only used to permit visual indication that the endpoint was near) and the amount of acid present was calculated.

Compounds inducing inhibition of gastric acid secretion of 20% or morewere considered active. In a representative operation, and merely by wayof illustration, the results obtained with this assay with a typicalcompound of the present invention are given in Table 2, below.

                  TABLE 2                                                         ______________________________________                                                    Intraduodenal                                                                 dose, mg./kg.   Percent                                           Compound    of body weight  Inhibition                                        ______________________________________                                        9-oxo-15-hydroxy-                                                             3,3-dimethyl-13-                                                              trans-prostenoic                                                              acid        100             51                                                ______________________________________                                    

Bronchodilator activity was determined in guinea pigs againstbronchospasms elicited by intravenous injections of 5-hydroxytryptamine,histamine or acetylcholine by the Koazett procedure. [See J. Lulling, P.Lievene, F. N1 Shayed and J. Prignot, Arzeimittel-Porschung, 18 995(1968).]

In the Table which follows bronchodilator activity for representativecompounds of this invention against one or more of the three spasmogenicagents is expressed as an ED₅₀ determined from the results obtained withthree logarithemic cumulative intravenous doses.

                  TABLE 2A                                                        ______________________________________                                        Bronchodilator Activity (Konzett Assays)                                      ED.sub.50, mg./kg.                                                                    Spasmogenic Agent                                                               5-hydroxy-                                                          Compound  tryptamine  histamine   choline                                     ______________________________________                                        9-oxo-15-hy-                                                                  droxy-16-ethyl-                                                               13-trans-pro-                                                                           --          81.3 × 10.sup.-6                                                                    --                                          stenoic acid                                                                  9-oxo-15-hy-                                                                  droxy-13-cis-                                                                           106 × 10.sup.-6                                                                     81.3 × 10.sup.-6                                                                    320 × 10.sup.-6                       prostenoic                                                                    acid                                                                          9-oxo-15-hy-                                                                  droxy-2-ethyl-                                                                          329 × 10.sup.-6                                                                     145 × 10.sup.-6                                                                     533 × 10.sup.-6                       13-trans-pro-                                                                 stenoic acid                                                                  9-oxo-15-hy-                                                                  droxy-16-pro-                                                                 stynoic acid                                                                            50.8 × 10.sup.-6                                                                    92.6 × 10.sup.-6                                                                    320 × 10.sup.-6                       ______________________________________                                    

The novel compounds of the present invention are useful as hypotensiveagents and their prostaglandin-like hypotensive activity wasdemonstrated in the following test procedure. This procedure is amodification of the technique described by Pike et al., Prostaglandins,Nobel Symposium 2, Stockholm, June, 1966; p. 165.

Male Wistar strain rats (Royal Hart Farms) averaging approximately 250grams in weight were fastened to rat boards in a supine position bymeans of canvas vests and limb ties. The femoral area was infiltratedsubcutaneously with lidocaine and the iliac artery and vein were exposedand cannulated. Arterial blood pressure (systolic/diastolic) wasrecorded using a Statham P₂₃ Db pressure, the animals were anethetizedbefore use with pentobarbital, 30 mg./kg. of body weight intravenously,and also were given hexamethoxium bitartrate, 2 mg./kg. of body weightintravenously. The test compounds were prepared by ultrasonic dispersionin a saline-Treen 80® vehicle. A constant intravenous dose volume of 0.5ml. was administered and test doses ranged from 0.1 to 10.0 mg./kg. ofbody weight. Increasing or decreasing doses were selected depending onthe dose response obtained. In Table 2B below are set forth the minimaldoses required to produce a decrease of about 10 mm. in diastolic bloodpressure for typical compounds of the present invention.

                  TABLE 2B                                                        ______________________________________                                        HYPOTENSIVE ACTIVITY                                                                            Minimal effective                                                             hypotensive dose                                            Compound          (mg./kg. of body wt.)                                       ______________________________________                                        2-ethyl-9-oxo-15-                                                             hydroxy-13-trans-pro-                                                         stenoic acid      <2                                                          2-ethyl-9-oxo-15-epi-                                                         hydroxy-13-trans-pro-                                                         stenoic acid      2-4                                                         2-ethyl-9-oxo-15-                                                             hydroxy-prostanoic                                                            acid              0.2                                                         2-methyl-9-oxo-15-epi-                                                        hydroxy-13-trans-pro-                                                         stenoic acid      2                                                           2-methyl-9-oxo-15-                                                            hydroxy-13-trans-pro-                                                         stenoic acid      2                                                           8β-methyl-9-oxo-15-                                                      hydroxy-13-trans-                                                             prostenoic acid   2                                                           9-oxo-15-hydroxy-16-                                                          ethyl-13-trans-pro-                                                           stenoic acid      <8                                                          3,3-dimethyl-9-oxo-15-                                                        hydroxy-13-trans-pro-                                                         stenoic acid      8                                                           9-oxo-15-hydroxy-13-cis-                                                      prostenoic acid   2-4                                                         9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid      <2                                                          9-oxo-15-hydroxy-16-                                                          prostynoic acid   2                                                           9-oxo-15-hydroxy-5-cis,                                                       13-trans,17-cis-prosta-                                                       trienoic acid     <2                                                          3-oxa-9-oxo-15-hydroxy-                                                       13-trans-prostenoic                                                           acid              <2                                                          3-oxa-9-oxo-15-epi-                                                           hydroxy-13-trans-pro-                                                         stenoic acid      1-2                                                         3-thia-9-oxo-15-hydroxy-                                                      13-trans-prostenoic                                                           acid              2                                                           3-thia-9-oxo-15-epi-                                                          hydroxy-13-trans-                                                             prostenoic acid   2                                                           9-oxo-15-hydroxy-16-                                                          trans-prostenoic acid                                                                           <2                                                          2-phenyl-9-oxo-15-                                                            hydroxy-13-trans-                                                             prostenoic acid   8                                                           2-phenyl-9-oxo-15-epi-                                                        hydroxy-13-trans-pro-                                                         stenoic acid      2-8                                                         2-fluoro-9-oxo-15-                                                            hydroxy-13-trans-pro-                                                         stenoic acid      8                                                           7a,7b-bishomo-9-oxo-15-                                                       hydroxy-13-trans-                                                             prostenoic acid   <8                                                          9-oxo-10a-homo-15-                                                            hydroxy-13-trans-pro-                                                         stenoic acid      2                                                           9-oxo-10a-homo-15-epi-                                                        hydroxy-13-trans-                                                             prostenoic acid   2                                                           9-oxo-15-hydroxy-15-                                                          methyl-5-cis,13-trans,                                                        17-cis-prostatrienoic                                                         acid              <2                                                          Ethyl 3-oxa-9-oxo-15-                                                         hydroxy-13-trans-                                                             prostenoate       0.2                                                         Ethyl 3-oxa-9-oxo-15-                                                         epi-hydroxy-13-trans-                                                         prostenoate       0.2                                                         Ethyl 9-oxo-10a-homo-                                                         15-hydroxy-13-trans-                                                          prostenoate       2                                                           9-oxo-15-hydroxy-16,16-                                                       dimethyl-13-trans-                                                            prostenoic acid   <2                                                          9-oxo-15-hydroxy-17,17-                                                       dimethyl-13-trans-                                                            prostenoic acid   2                                                           3-thia-9-oxo-15-hydroxy-                                                      16,16-dimethyl-13-                                                            trans-prostenoic acid                                                                           <2                                                          3-oxa-9-oxo-15-hydroxy-                                                       16,16-dimethyl-13-                                                            trans-prostenoic acid                                                                           <2                                                          ______________________________________                                    

This invention will be described in greater detail in conjunction withthe following specific examples. In these examples it is to be notedthat Example 724 follows directly after Example 699.

In the examples which follow reference to 15-hydroxy or 15-oxyderivatives, unless otherwise indicated is inclusive of both the 15-epiand 15-normal racemates. In addition, all possible antipodes resultingfrom asymetry at C₈, C₁₂ and elsewhere in the prostenoic acid moleculeare included.

EXAMPLE 1 Preparation of2-carbalkoxy(methyl/ethyl)-2-(4-carbethoxybutyl)-cyclopentan-1-one

To a stirred solution of the sodium cyclopentanone carboxylate enolatein dimethoxyethane, prepared from 187 g. (1.248 moles) of2-cyclopentanone carboxylate (mixed methyl and ethyl esters), 52.4 g.(1.248 moles) sodium hydride (57.2% in mineral oil) and 1.6 l. ofdimethoxyethane, is added dropwise 309 g. (1.212 moles) of ethyl5-iodovalerate. The reaction mixture is stirred and heated at reflux for18 hours. The mixture was cooled and filtered. The solvent is removedfrom the filtrate by evaporation and the residue is poured into dilutehydrochloric acid and extracted with ether. The combined extracts arewashed with water and saline, dried over magnesium sulfate andevaporated to give an oil. The oil is distilled under reduced pressureto give 274 g. of a light yellow oil, b.p. 140°-143° C. (0.17 mm).

EXAMPLE 2 Preparation of 2-(4-carboxybutylcyclopentan-1-one

A stirred mixture of 274 g. of 2-carbalkoxy(mixed methyl and ethylesters)-2-(4-carbethoxybutyl)cyclopentan-1-one (Example 1), 600 ml. of20% hydrochloric acid and 325 ml. of acetic acid is heated at reflux for20 hours. Solution occurs in approximately 1/2 hour. The solution iscooled and diluted with water and extracted with ether. The combinedextracts are washed with saline and dried over magnesium sulfate andevaporated. The residue is evaporated twice with toluene to give 144 g.of an oil.

EXAMPLE 3 Preparation of 2-(4-carbethoxybutyl)cyclopentan-1-one

A stirred solution of 124 g. (0.673 mole) of2-(4-carboxybutyl)cyclopentan-1-one (Example 2), 800 ml. of ethanol and1 g. of p-toluenesulfonic acid monohydrate is heated at reflux for 18hours. The solvent is evaporated and the residue is dissolved in ether.The ether solution is washed with saline, diluted sodium bicarbonatesolution and again with saline, dried over magnesium sulfate andevaporated. The oil is distilled under reduced pressure to give 149 g.of a colorless oil, b.p. 106°-109° C. (0.23 mm).

EXAMPLE 4 Preparation of2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 1, treatment of 2-cyclopentanonecarboxylate (mixed methyl and ethyl esters) with sodium hydride indimethoxyethane followed by ethyl 4-iodobutyrate gives a yellow oil,b.p. 137° C. (0.16 mm).

EXAMPLE 5

Preparation of 2-(3-carboxypropyl)cyclopentan-1-one

In the manner described in Example 2, treatment of 2-carbalkoxy(mixedmethyl and ethyl esters)-2-(3-carbethoxypropyl)cyclopentan-1-one(Example 4) with a 20% hydrochloric acid and acetic acid mixture gives ayellow oil.

EXAMPLE 6 Preparation of 2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 3, treatment of2-(3-carboxypropyl)cyclopentan-1-one (Example 5) with p-toluenesulfonicacid monohydrate in ethanol gives a colorless oil, b.p. 93° C. (0.10mm).

EXAMPLE 7 Preparation of ethyl and methyl2-(6-carbethoxyhexyl)-1-cyclopentanon-2-carboxylate

In the manner described in Example 1, ethyl and methyl 2-cyclopentananecarboxylate is reacted with ethyl 7-bromoheptanoate to furnish thesubject product, b.p. 147° C. (0.09 mm).

EXAMPLE 8 Preparation of 2-(6-carboxyhexyl)cyclopentan-1-one

In the manner described in Example 2, ethyl and methyl2-(6-carbethoxyhexyl)-1-cyclopentanone-2-carboxylate (Example 7) ishydrolyzed to furnish the subject product, b.p. 143° C. (0.05 mm).

EXAMPLE 9 Preparation of 2-(6-carbethoxyhexyl)cyclopentan-1-one

In the manner described in Example 3,2-(6-carboxyhexyl)cyclopentan-1-one (Example 8) is esterified to furnishthe subject product, b.p. 110° C. (0.03 mm).

EXAMPLE 10 Preparation of 1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-one

A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)cyclopentan-1-one(Example 9) in 250 ml. of acetic anhydride containing 0.940 g. ofp-toluenesulfonic acid monohydrate is heated to boiling under partialreflux allowing distillate at 118° C. or less (i.e., acetic acid) toescape through a Vigreaux column equipped with a condenser to collectthe distillate. After 16 hours, during which period acetic anhydride isadded in portions in order to keep the solvent level at at least 100ml., the solution is cooled and poured cautiously into a stirred coldmixture of saturated sodium bicarbonate solution (400 ml.) and hexane(250 ml.). The resulting mixture is stirred for an additional 30 minutesduring which period solid sodium bicarbonate is added periodically toinsure a basic solution. The hexane layer is separated and washed withsaturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness. Distillation of the residual oil gives 102g. (87%) of pale yellow oil, b.p. 118° C. (0.07 mm).

EXAMPLE 11 Preparation of1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-one

In the manner described in Example 10, treatment of2-(3-carbethoxypropyl)cyclopentan-1-one (Example 6) with aceticanhydride and p-toluenesulfonic acid monohydride gives a yellow oil,b.p. 98°-103° C. (0.35 mm).

EXAMPLE 12 Preparation of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-one

In the manner described in Example 10, treatment of2-(4-carbethoxybutyl)cyclopentan-1-one (Example 3) with acetic anhydrideand p-toluenesulfonic acid monohydrate gives a yellow oil, b.p.109°-110° C. (0.37 mm).

EXAMPLE 13 Preparation of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 50 g. of1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-one (Example 10) in 150 ml.of chloroform, 200 ml. of water and 18.8 g. of calcium carbonate, cooledin an ice bath, is added dropwise over a period of about 30 minutes, asolution of 30 g. of bromine in 50 ml. of carbon tetrachloride. Afterstirring for an additional 45 minutes the chloroform layer is separatedand washed successively with dilute sodium thiosulfate solution,saturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness under reduced pressure.

The residual oil is dissolved in 50 ml. of N,N-dimethylforamide andadded to a mixture of 33 g. of lithium bromide and 32 g. of lithiumcarbonate in 375 ml. of N,N-dimethylformamide, previously dried byrefluxing with 375 ml. of benzene under a Dean-Stark apparatus followedby distillation of the benzene. The mixture is stirred at the refluxtemperature for 30 minutes, then cooled and poured into 850 ml. ofice-cold water. The resulting mixture is acidifed (cautiously) with 4Nhydrochloric acid and extracted with ether three times. The combinedother extracts are washed with saturated sodium chloride solution, driedwith anhydrous magnesium sulfate and taken to dryness under reducedpressure to afford 41.5 g. of an amber oil. In order to convert anyisomeric material to the desired product, 41.5 g. of the above materialis treated with 0.500 g. of p-toluenesulfonic acid monohydrate in 450ml. of absolute alcohol at the reflux temperature for 18 hours. Thesolution is taken to dryness under reduced pressure. The resulting gumis dissolved in ether and washed with saturated sodium bicarbonatesolution, saturated sodium chloride solution, dried with anhydrousmagnesium sulfate and taken to dryness under reduced pressure. Theresidual oil is distilled to give 30.2 g. of product; b.p. 118° C. (0.05mm); λ_(max) ^(MeOH) 229 μ(E9950): λ_(max) 5.75, 5.85, 6.15, 8.45μ;vapor phase chromatography shows 99% product, containing 1%2-(6-carboethoxyhexyl)cyclopentan-1-one.

This product can be purified by the following procedure. A mixture of120 g. of 2-(6-carbethoxyhexyl)-2-cyclopentenone, containingapproximately 5% of the saturated analogue, and 7.67 g. (10 molepercent) of p-carboxyphenylhydrazine in 400 ml. of absolute ethanol isstirred at ambient temperature for 18 hours and is then refluxed for 1hour. The mixture is cooled, the solvent is evaporated, and the residueis taken up into 150 ml. of chloroform and passed through a column of450 g. of aluminum oxide (Merck). The filtrate is evaporated to yield acolorless oil containing (0.5% of the saturated impurity.

EXAMPLE 14 Preparation of 2-(3-carbethoxypropyl)cyclopent-2-en-1-one

In the manner described in Example 13, bromination of1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-ene (Example 11) followed bydehydrobromination with lithium bromide and lithium carbonate isproductive of the subject compound.

EXAMPLE 15 Preparation of 2-(4-carbethoxybutyl)cyclopent-2-en-1-one

In the manner described in Example 13, treatment of1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene (Example 12) with bromineand subsequent treatment of the brominated product with a mixture oflithium bromide and lithium carbonate in N,N-dimethylformamide isproductive of the subject compound. Treatment of this product withp-carboxyphenylhydrazine by the procedure of Example 13 furnishes aproduct which contains less than 0.5% of the corresponding saturatedketone.

EXAMPLE 16 Preparation of1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene

To a mixture of 35.97 g. (0.151 mole) of2-(6-carbethoxyhexyl)-2-cyclopentenone (Example 13) and 15.0 g. (0.180mole) of methoxyamine hydrochloride in 300 ml. of absolute ethanol isadded 25 ml. of pyridine and the resulting solution is stirred for 20hours at ambient temperatures. The solvent is evaporated and the residueis partitioned between water and diethyl ether. The organic phase iswashed with water and saturated brine, dried (Na₂ SO₄), and the solventis evaporated to yield an oil. Distillation yields 38.7 g. of acolorless oil, b.p. 115°-118° C. (0.075 mm). IR (film): 1740, 1627,1053, 890 cm⁻¹. λ_(max) (MeOH) 243 (13,000). NMR δ (CDCl₃): 3.89.

EXAMPLE 17 Preparation of1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene

To an ice cooled solution of 34.10 g. (0.128 mole) of1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene (Example 16) in 200ml. of benzene under nitrogen is added dropwise 225 ml. of a 25%solution of diisobutyl aluminum hydride in hexane. The resultingsolution is stirred for 2 hours at 0°-5° C., poured onto ice and dilutehydrochloric acid, and the aqueous phase is saturated with sodiumchloride. The organic phase is separated, washed with saturated brine,dried (Na₂ SO₄), and evaporated to yield an oil. The latter is dissolvedin 100 ml. of hot hexane and cooled to yield 24.3 g. of crystals, m.p.62°-64° C. IR (KBr) 3260, 1630, 1059, 893 cm⁻¹. λ_(max) 243 (14,200).NMR (CDCl₃)δ: 2.37.

EXAMPLE 18 Preparation of1-methoximino-2-(7-p-toluenesulfonyloxyheptyl)-2-cyclopentene

To a solution of 5.00 g. (0.0222 mole) of1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene (Example 17) in 50 ml.of dry pyridine at 0° C. is added 8.45 g. (0.0444 mole) ofp-toluenesulfonyl chloride and the resulting solution is chilled at 5°C. overnight. The mixture is partitioned between 300 ml. of ice waterand diethyl ether. The organic phase is washed with 1:1 ice coldhydrochloric acid, cold water, and cold saturated brine, dried (NaSO₄/K₂ CO₃), and evaporated under reduced pressure at room temperature toyield an oil. The latter is dissolved in 600 ml. of hexane, treated with0.5 g. of Darco, filtered and evapoated to yield 7.7 g. of a colorlessoil. IR (film) 1600, 1192, 1182, 1053, 890 cm⁻¹.λ_(max) (MeOH) 228 and243.

EXAMPLE 19 Preparation of1-methoximino-2-(8,8-dicarbethoxyoctyl)-2-cyclopentene

To an alcoholic solution of sodiodiethyl malonate, prepared from 0.847g. (0.0368 g. atoms) of sodium, 100 ml. of absolute ethanol, and 7.05 g.(0.0440 mole) of diethyl malonate is added 7.7 g. of the tosylate ofExample 18 and the mixture is refluxed for 2 hours under a nitrogenatmosphere. The mixture is partitioned between cold dilute hydrochloricacid and diethyl ether, and the organic phase is washed with water andsaturated brine, dried (Na₂ SO₄), and evaporated to yield an oil. Theexcess diethyl malonate is distilled off under reduced pressure to yield6.45 g. of a yellowish oil. IR (film) 1755, 1728, 1625, 1054, 890 cm⁻¹.

EXAMPLE 20 Preparation of1-methoximino-2-(8,8-dicarboxyoctyl)-2-cyclopentene

A mixture of 6.45 g. of the diester of Example 19 and 6.72 g. ofpotassium hydroxide in 150 ml. of 1:1 aqueous methanol is refluxed for 1hour, cooled, and is partitioned between water and diethyl ether. Theaqueous phase is acidified with hydrochloric acid, extracted with ether,and the organic phase is washed with water and saturated brine, dried(Na₂ SO₄) and evaporated to yield a solid. The solid is crystallizedfrom benzene to yield 4.15 g. of tan crystals, m.p. 135°-137° C. (-CO₂).

EXAMPLE 21 Preparation of1-methoximino-2-(8-carboxyoctyl)-2-cyclopentene

A solution of 3.926 g. (0.0126 mole) of the diacid of Example 20 in 20ml. of xylene is refluxed for 1.5 hours, cooled, and evaporated to yielda tan solid. IR (KBr) 1720, 1618, 1179, 1050, 986 cm⁻¹.

EXAMPLE 22 Preparation of 2-(8-carboxyoctyl)cycopent-2-en-1-one

The acid methoxime from Example 21 is refluxed for 5 hours with 55 ml.of acetone and 20 ml. of 2N hydrochloric acid. The mixture is cooled,the solvent is evaporated, and the residue is partitioned between waterand diethyl ether. The organic phase is washed with water and saturatedbrine, dried (Na₂ SO₄), and evaporated to yield a tan solid. IR (KBr)1745, 1665 cm³¹ 1.λ_(max) (MeOH) 228 (12,600).

EXAMPLE 23 Preparation of 2-(8-carboxyoctyl)cyclopent-2-en-1-one

The acid ketone from Example 22 is Fisher esterified with 100 ml. ofabsolute ethanol, 100 ml. of benzene, and 20 mg. of p-toluenesulfonicacid for 6 hours, cooled, and the solvent is evaporated. The resultingoil is dissolved in 3:1 benzene-ether and the solution is passed througha column of 100 g. of Florisil®. The filtrate is evaporated and theresidue is distilled to yield 2.97 g. of a colorless oil, b.p. 137°-139°C. (0.05 Torr).

EXAMPLE 24 Preparation of 2-(4-carbethoxybutyl)-2-cyclopentenonemethoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenone (Example 15) withmethoxyamine hydrochloride in the manner described in Example 16 givesan oil, b.p. 107°-109° C. (0.05 mm). IR (film): 1740, 1628, 1050, 885cm⁻¹.λ_(max) (MeOH) 243 (13,600).

EXAMPLE 25 Preparation of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopenteno-methoxime (Example 24)with diisobutyl aluminum hydride in the manner described in Example 17gives crystals, m.p. 33°-35° C. IR (KBr) 3420, 1630, 1050, 886cm⁻¹.λ_(max) ^(MeOH) 243 (12,020).

EXAMPLE 26 Preparation of2-(5-p-toluenesulfonyloxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime (Example 25)with p-toluenesulfonyl chloride in pyridine in the manner described inExample 18 gives a colorless oil. IR (film) 1600, 1190, 1180, 1050, 885cm⁻¹.

EXAMPLE 27 Preparation of 2-(6,6-dicarbethoxyoctyl)-2-cyclopentenonemethoxime

To a solution of sodio diethyl ethylmalonate, prepared from 1.63 g.(0.0387 mole) of sodium hydride in mineral oil (57.2%), 100 ml. ofethylene glycol dimethyl ether and 8.5 g. (0.0452 mole) of ethyl diethylmalonate, is added 7.5 g. of tosylate from Example 26 in 20 ml. ofethylene glycol dimethyl ether and the mixture is refluxed for 3 hoursand then allowed to stand at room temperature for 18 hours undernitrogen atmosphere. The reaction mixtute is filtered and most of thesolvent is removed. The mixture is partitioned between cold dilutehydrochloric acid and diethyl ether, and the organic phase is washedwith water and saturated brine, dried (MgSO₄), and evaporated to yieldan oil. The excess ethyl diethyl malonate is distilled off under reducedpressure to yield 6.7 g. of a yellow oil. IR (film) 1755, 1728, 1627,1050, 885 cm⁻¹.

EXAMPLE 28 Preparation of 2-(6,6-dicarboxyoctyl)-2-cyclopentenonemethoxime

Treatment of 2-(6,6-dicarbethoxyoctyl)-2-cyclopenteno methoxime (Example26) with potassium hydrixide, and 1:1 aqueous methanol in the mannerdescribed in Example 20 gives a light yellow oil.

EXAMPLE 29 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime

In the manner described in Example 21, treatment of2-(6,6-dicarboxyoctyl)-2-cyclopentenone methoxime (Example 28) withxylene at reflux for 18 hours gives a yellow oil.

EXAMPLE 30 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime (Example 29)with acetone and 2 N hydrochloric acid in the manner described inExample 22 gives a light yellow oil.

EXAMPLE 31 Preparation of 2-(6-carbethoxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone (Example 30) withthionyl chloride and then treatment of the acid chloride with ethanol inthe usual manner gives an amber oil. The oil is placed on amagnesia-silica gel column and eluted with 3:1 benzene:ether. Thesolvent is removed and the residue is distilled, b.p. 122° C. (0.06 mm).

EXAMPLE 32 Preparation of diethyl1,1-dimethyl-5-tetrahydropyranylpentylmalonate

To 486 mg. (0.02 g.-atoms) of magnesium in 5 ml. of toluene containingone molar equivalent of tetrahydrofuran per equivalent of magnesium andone percent iodine (calculated in weight of magnesium) is added dropwise3.86 g. (0.02 mole) of 4-chloro-1-tetrahydropyranyloxybutane over aperiod of one hour with stirring, under nitrogen at 70° C. The reactionmixture is stirred at 70° C. for four hours. This reagent is then addeddropwise to 3 g. (0.015 mole) of ethyl isopropylidenemalonate in 40 ml.of tetrahydrofuran containing 392 mg. of tetrakis[iodo(tri-n-butylphosphine)copper (I)] and stirred at room temperaturefor 2 hours. The reaction mixture is poured into cold dilutehydrochloric acid and extracted with ether. The ether extract is driedover magnesium sulfate and concentrated to give 5.92 g. of subjectproduct as an oil.

EXAMPLE 33 Preparation of diethyl 1,1-dimethyl-5-hydroxypentylmalonate

A solution of 3.5 g. (0.01 mole) of diethyl1,1-dimethyl-5-tetrahydrofuranyloxypentylmalonate in 70 ml. of ethanolcontaining 3 ml. of hydrochloric acid is allowed to stir at roomtemperature for 18 hours. The solution is concentrated, diluted withwater and extracted with ether. The ether extract is washed with water,dried over magnesium sulfate and concentrated to give 3.262 g. of alight yellow oil. The oil is purified by distillation, b.p. 116°-117° C.(0.05 mm).

EXAMPLE 34 Preparation of 3,3-dimethyl-7-hydroxyheptanoic acid

A mixture of 32 g. (0.117 mole) of diethyl1,1-dimethyl-5-hydroxypentylmalonate, 25 g. of potassium hydroxide and600 ml. of methanol-water (1:1) is heated at reflux for 8 hours and thenallowed to stand at room temperature for 18 hours. The methanol isremoved, diluted with water and the reaction mixture is acidified withconcentrated hydrochloric acid. The mixture is extracted with ether. Theextract is washed with water and saline, dried over anhydrous magnesiumsulfate and concentrated to give 27 g. of1,1-dimethyl-5-hydroxypentylmalonic acid. This crude oil is dissolved in200 ml. of bis-(2-methoxyethyl)ether and is heated at reflux for 4 hoursand then allowed to stand at room temperature overnight. The solvent isremoved and the reaction mixture is diluted with water and extractedwith ether. The organic solution is washed with saline, dried overmagnesium sulfate and concentrated to give 18 g. of product as an oil.

EXAMPLE 35 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3.484 g. (0.02 mole) of 3,3-dimethyl-7-hydroxyheptanoicacid in 25 ml. of chloroform containing 3 drops of dimethylformamide isadded 5.8 ml. (0.08 mole) of thionyl chloride and the solution is thenheated at reflux for 3-4 hours. The solution is concentrated to give theintermediate 3,3-dimethyl-7-chloro-1-heptanoyl chloride. The acidchloride is dissolved in a minimum amount of benzene and added slowly to20 ml. benzene, 10 ml. of ethanol and 2.65 ml. of collidine. Thesolution is heated at reflux for one hour and then concentrated. Theresidue is dissolved in ether, washed with water, dilute sodiumbicarbonate solution and saline. The organic solution is dried overmagnesium sulfate and concentrated to give 3.57 g. of product as ayellow oil.

EXAMPLE 36 Preparation of ethyl 3,3-dimethyl-7-iodoheptanoate

To a solution of 3.57 g. (0.0162 mole) of ethyl3,3-dimethyl-7-chloroheptanoate in 100 ml. of methyl ethyl ketone isadded 4 g. of sodium iodide and the mixture heated at reflux for 18hours. The reaction mixture is cooled, filtered and concentrated. Theresidue is partitioned between ether and water. The aqueous phase isextracted several times with ether. The extract is washed with sodiumbisulfite solution, water and saline. The organic solution is dried overmagnesium sulfate and concentrated to give 4.182 g. of a yellow oil. Thematerial is purified by distillation, b.p. 86°-87° C. (0.18 Torr).

EXAMPLE 37 Preparation of2-carbalkoxy(methyl/ethyl)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by treatment of sodio cyclopentanonecarboxylate enolate with ethyl 3,3-dimethyl-7-iodoheptanoate by theprocedure described in Example 1.

EXAMPLE 38 Preparation of2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by decarbalkoxylation of 2-carbalkoxy (mixedmethyl and ethylester)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one by theprocedure described in Example 2.

EXAMPLE 39 Preparation of2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

Esterification of 2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one withethanol by the procedure described in Example 3 is productive of thesubject compound.

EXAMPLE 40 Preparation of1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene

This compound is prepared from2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one and acetic anhydrideby the process described in Example 10.

EXAMPLE 41 Preparation of2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

This compound is prepared from1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene viabromination and dehydrobromination according to the procedure describedin Example 13.

EXAMPLE 42 Preparation of2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example16, 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene is prepared from2-(3-carbethoxypropyl)-2-cyclopentenone (Example 14) and methoxyaminehydrochloride.

EXAMPLE 43 Preparation of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example17, 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene is prepared from2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene anddiisobutylaluminum hydride.

EXAMPLE 44 Preparation of2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 4.833 g. (0.0266 mole) of2-(4-hydroxypentane)-1-methoximino-2-cyclopentene in 50 ml. of drytetrahydrofuran under nitrogen is added 16.7 ml. of 1.6 molar n-butyllithium in hexane, dropwise. The reaction mixture is stirred for 0.5hour and then 4.85 g. (0.029 mole) of ethyl bromoacetate is addeddropwise. The reaction mixture is stirred overnight at room temperatureand then refluxed for 1.5 hours. The reaction is cooled and poured intowater and extracted several times with ether. The ether extracts arewashed with saline, dried over magnesium sulfate, and concentrated. Theresidue is placed on an alumina column, chloroform being used as a washsolvent. The combined washings are concentrated to dryness to give 4.903g. of product as a yellow oil.

EXAMPLE 45 Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene with acetoneand 2 N hydrochloric acid at reflux gives the subject compound as ayellow oil.

EXAMPLE 46 Preparation of 2-(6-carbethoxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 23, treatment of2-(6-carboxy-5-oxahexyl)-2-cyclopentenone with p-toluenesulfonic acid inethanol produces the subject product as a light yellow oil.

EXAMPLE 47 Preparation of2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 3.66 g. (0.02 mole) of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene (Example 43) in 50 ml.of 1,2-dimethoxyethane under nitrogen is added dropwise 17 ml. of 1.6 Mn-butyl lithium in hexane. The reaction mixture is stirred for half anhour and then the lithium salt of chloroacetic acid, prepared from 1.89g. (0.02 mole) of chloroacetic acid and 16 ml. of 1.6 M n-butyl lithiumin 20 ml. of dimethoxyethane, is added and the reaction mixture isheated at reflux for 48 hours. The solvent is evaporated and the residueis partitioned between ether and water. The aqueous phase is acidifiedwith hydrochloric acid and extracted with ether. The organic phase iswashed with water and saturated saline solution, dried (MgSO₄), andevaporated to give 3.35 g. of a yellow oil.

EXAMPLE 48 Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopenten-1-one

In the manner described in Example 22, treatment of2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene (Example 47) withacetone and 2 N hydrochloric acid at reflux gives the subject compoundas a yellow oil.

EXAMPLE 49 Preparation of1-methoximino-2-(4-methanesulfonyloxybutyl)-2-cyclopentene

To a solution of 1.83 g. (0.01 mole) of1methoximino-2-(4-hydroxybutyl-2-cyclopentene (Example 43) in 10 ml. ofmethylene chloride containing 1.52 g. (0.015 mole) of triethylamine isadded 1.265 g. (0.011 mole) of methanesulfonyl chloride over a period of5-10 minutes at -10°-0° C. Stirring is continued for 15 minutes and thesolution is then washed with cold water, cold 10% hydrochloric acid,cold sodium bicarbonate solution, and cold saline solution. The organicphase is dried (MgSO₄) and concentrated to give an oil which solidifiesupon cooling. Crystallization from ether-petroleum ether (30°-60° C.)gives 1.797 g. of white crystals, m.p. 67°-68° C.

EXAMPLE 50 Preparation of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene

A mixture of 2.75 g. (0.01 mole) of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60)and 1.47 g. (0.03 mole) of sodium cyanide in 20 ml. of dryN,H-dimethylformamide is heated at 65°-70° C. for 3 hours. The cooledreaction mixture is poured into water and extracted with diethyl ether.The organic phase is washed with water and saturated saline solution,dried (MgSO₄), and evaporated to give 1.89 g. of a light yellow oil.

EXAMPLE 51 Preparation of1-methoximino-2-(5-carboxypentyl)-2-cyclopentene

A mixture of 1.89 g. (0.0092 mole) of1-methoximino-2-(5-cyanopentyl)-2-cyclopentene (Example 50) and 1 g.(0.025 mole) of sodium hydroxide in 50 ml. of 1:1 aqueous-ethanol isrefluxed for 48 hours, cooled, and partitioned between water and diethylether. The aqueous phase is acidified with hydrochloric acid, extractedwith diethyl ether, and the organic phase is washed with water andsaturated saline solution, dried (MgSO₄), and evaporated to give 1.86 g.of a yellow oil.

EXAMPLE 52 Preparation of 2-(5-carboxypentyl)-2-cyclopentenone

A solution of 1.86 g. (0.00825 mole) 1-methoximino-2-(5-carboxypentyl)-2-cyclopentene (Example 51) in 44 ml. of acetone and13.1 ml. of 2N hydrochloric acid is refluxed for 5 hours. The solvent ispartially evaporated and a solid precipitates and is collected. Theresidue is extracted with diethyl ether and the organic phase is washedwith saturated saline solution, dried (MgSO₂), and evaporated to yieldadditional solid. The combined solid material is crystallized fromether/pet ether (30°-60° C.) to yield crystalline material, m.p. 70°-72°C.

EXAMPLE 53 Preparation of 2-(5-carbethoxypentyl)-2-cyclopentenone

A solution of 1.309 g. (0.00668 mole) of2-(5-carboxypentyl)-2-cyclopentenone (Example 52) and 90 mg. ofp-toluenesulfonic acid in 150 ml. of ethanol is refluxed for 18 hours.The solvent is evaporated and the residue is dissolved in ether. Theorganic phase is washed with water, sodium bicarbonate solution, andsaturated saline solution, dried (MgSO₄), and evaporated to give 1.371g. of a light yellow oil.

EXAMPLE 54 Preparation of2-(5-acetoxypentyl)-2-carbomethoxy/carbethoxy-cyclopentanone

A mixture of sodiocyclopentanone carboxylate, prepared from 1200 g. (8.0moles) of cyclopentanone carboxylate (methyl and ethyl esters) and 200g. (8.3 moles) of mineral oil free sodium hydride in 10 . of1,2-dimethoxyethane, 1320 g. (8.0 moles) of 5-chloro-1-amyl acetate[M.E. Synerholm, Journ. Amer. Chem. Soc., 69, 2681 (1947)], and 1200 g.(8.0 moles) of sodium iodide is refluxed under nitrogen for 18 hours.The mixture is cooled, concentrated to 4 l. and partitioned betweendilute hydrochloric acid and diethyl ether. The organic phase is washedwith water and saturated brine, dried (MgSO₄), and evaporated to yield1920 g. of an oil.

EXAMPLE 55 Preparation of2-(5-hydroxypentyl)cyclopentanone/2-(5-acetoxy-pentyl)-cyclopentanone

A mixture of 4,500 g. (16.2 moles) of2-(5-acetoxypentyl)-2-carbomethoxy/carboethoxy-cyclopentanone (Example54), 2.2 1. of glacial acetic acid, 1 l. of concentated hydrochloricacid, and 1 l. of water is refluxed for 18 hours, cooled, andpartitioned between saturated brine and benzene. The organic phase iswashed with saturated brine, dried (MgSO₄), and evaporated in vacuo toyield 3155 g. of an oil.

EXAMPLE 56 Preparation of 1-acetoxy-2-(5-acetoxypentyl)-1-cyclopentene

A solution of 400 g. (2.04 moles) of a mixture of2-(5-hydroxypentyl)cyclopentanone and 2-(5-acetoxypentyl)cyclopentanone(Example 55) and 4.0 g. of p-toluenesulfonic acid monohydrate in 1 1. ofacetic anhydride is refluxed at a rate to maintain a steady distillationof acetic acid from the reaction through a helix-packed fractionationcolumn. The reaction is continued with the addition of acetic anhydrideto maintain a constant volume until complete conversion of startingmaterials to product is evident. The mixture is cooled and partitionedbetween 2 1. of hexane and 3 1. of cold water containing solid sodiumbicarbonate to maintain a neutral pH. The organic phase is washed withsaturated brine, dried (MgSO₄), and evaporated to yield 452 g. of anoil.

EXAMPLE 57 Preparation of 2-(5-acetoxypentyl)-2-cyclopentenone

To a well stirred mixture of 405 g. (4.05 moles) of calcium carbonate,31. of water, and 2.5 1. of chloroform cooled to 5° C. is addedsimultaneously 1016 g. (4.0 moles) of1-acetoxy-2-(5-acetoxy-pentyl)-1-cyclopentene (Example 56) and asolution of 648 g. (4.05 moles) of bromine in 500 ml. of carbontetrachloride at a rate to maintain a temperature below 10° C. Themixture is stirred for half an hour after addition of the reagents andthe phases are then separated. The organic phase is washed with 2%sodium thiosulfate solution, water, and saturated brine, dried (MgSO₄),and evaporated in vacuo to an oil. The oil is immediately added to arefluxing slurry of 500 g. (5.0 moles) of calcium carbonate in 2.5 1 ofN,N-dimethylacetamide under nitrogen and the mixture is then refluxedfor thirty minutes. The mixture is cooled, filtered, and partitionedbetween water and diethyl ether. The organic phase is washed with waterand saturated brine, dried (MgSO₄), and evaporated to yield 757 g. of anoil, b.p. 116°-118° C. (0.25 mm.).

EXAMPLE 58 Preparation of1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene

In the manner described for Example 16,2-(5-acetoxypentyl)-2-cyclopentenone (Example 57) is treated withmethoxyamine hydrochloride in pyridine and ethanol to yield the subjectcompound, b.p. 101°-103° C. (0.20 mm.).

EXAMPLE 59 Preparation of1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene

A mixture of 74 g. (0.22 mole) of1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene (Example 58) and 56 g.(1.0 mole) of potassium hydroxide in 300 ml. of 1:1 aqueous methanol isrefluxed for 2 hours and then cooled. The solvent is partially removedin vacuo and the residue is partitioned between saturated brine anddiethyl ether. The organic phase is washed with saturated brine, dried(MgSO₄), and evaporated to yield an oil which crystallized, m.p. 35°-36°C.

EXAMPLE 60 Preparation of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene

To a cold solution of 9.85 g. (0.05 mole) of1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene (Example 59) and 7.6 g.(0.075 mole) of triethylamine in 100 ml. of methylene chloride at -10°C. is added 6.3 g. (0.055 mole) of methanesulfonyl chloride at a rate tomaintain a temperature of -10° to 0° C. The mixture is then stirred for15 minutes and then poured into ice water. The organic phase is washedwith cold 10% hydrochloric acid, cold saturated sodium bicarbonatesolution, and cold saturated brine, dried (MgSO₄), and evaporated toyield a solid, m.p. 78°-80° C.

EXAMPLE 61 Preparation of1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene

To a suspension of sodiodiethylmalonate in 1,2-dimethoxyethane, preparedfrom 248 g. (1.55 moles) of diethyl malonate and 17.2 g. (0.95 mole) ofmineral oil free sodium hydride in 1 1. of 1,2-dimethoxyethane undernitrogen, is added 170 g. (0.62 mole) of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60)in 1.5 1. of 1,2-dimethoxyethane and the mixture is refluxed for 5hours. The mixture is cooled, filtered, and the solvent is evaporated.The residue is partitioned between cold dilute hydrochloric acid andwater, and the organic phase is washed with saturated brine, dried(MgSO₄), and evaporated to remove solvent and excess diethyl malonate toyield 209 g. of an oil.

EXAMPLE 62 Preparation of1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene

In the manner described in Example 20,1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene is treated withpotassium hydroxide in 1:1 aqueous methanol and then hydrochloric acidto yield the desired compound as crystals from diethyl ether, m.p.110°-115° C.

EXAMPLE 63 Preparation of1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene

A solution of 141 g. (0.50 mole) of1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene in 500 ml. ofbis-(2-methoxyethyl) ether is refluxed for 2 hours, cooled, andevaporated to yield an oil. The latter is crystallized from hexane toyield 92 g. of solid, m.p. 70°-72° C.

EXAMPLE 64 Preparation of 2-(6-carboxyhexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene (Example 63) withacetone and 2N hydrochloric acid at reflux provides the subjectcompound.

EXAMPLE 65 Preparation of 2-(6-carbethoxyhexyl)-2-cyclopentenone

Fischer estification of 2-(6-carboxyhexyl)-2-cyclopentenone (Example 64)in the manner of Example 23 provides the subject compound.

EXAMPLE 66 Preparation of1-methoximino-2-(G-fluoro-6,6-dicarbethoxyhexyl)-2-cyclopentene

To a solution of sodiodiethyl fluoromalonate, prepared from 2.002 g.(0.0491 mole) of sodium hydride in mineral oil (57.2%), 40 ml. of dryN,N-dimethylformamide and 8.174 g. (0.0458 mole) of diethylfluoromalonate is added dropwise 11.32 g. (0.0413 mole) of1-methoximino-2-(5-methylsulfonyloxypentyl)-2-cyclopentene (Example 60)in 60 ml. of N,N-dimethylformamide. The mixture is refluxed for 2 hoursunder a nitrogen atmosphere. The mixture is concentrated and partitionedbetween cold dilute hydrochloric acid and diethyl ether, and the organicphase is washed with saturated brine, dried (MgSO₄), and evaporated toyield 13.631 g. (92%) of a yellow oil.

EXAMPLE 67 Preparation of 1-methoximino-2-(6-fluoro,6,6-dicarboxyhexyl)-2-cyclopentene

A mixture of 13.631 g. of the diester of Example 66 and 16 g. ofpotassium hydroxide in 364 ml. of 1:1 aqueous methanol is refluxed for 5hours, cooled, concentrated, and is partitioned between water anddiethyl ether. The aqueous phase is acidified with hydrochloric acid,extracted with ether, and the organic phase is washed with saturatedbrine, dried (MgSO₄) and evaporated to yield a solid. The solid iscrystallized from diethyl ether petroleum ether (30°-60° C.) to give 10g. (90%) of white crystals, m.p. 143°-145° C. (-CO₂).

EXAMPLE 68 Preparation of1-methoximino-2-(6-fluoro-6-carboxyhexyl)-2-cyclopentene

A solution of 10 g. of the diacid of Example 67 in 60 ml. of2-methoxyethyl ether is refluxed for 7 hours, cooled, and evaporated toyield 8.5 g. (95%) of a tan solid. A sample is crystallized from diethylether-petroleum ether (30°-60° C.) to give white crystals, m.p. 98°-100°C.

EXAMPLE 69 Preparation of2-(6-fluoro-6-carboxyhexyl)cyclopent-2-en-1-one

The acid methoxime (8.5 g.) from Example 68 is refluxed for 5 hours with180 ml. of acetone and 64 ml. of 2N hydrochloric acid. The mixture iscooled, the solvent is evaporated, and the residue is partitionedbetween water and diethyl ether. The organic phase is washed withsaturated brine, dried (MgSO₄) and evaporated to yield 7.4 g. (98%) of alight yellow oil.

EXAMPLE 70 Preparation of2-(6-fluoro-6-carbethoxyhexyl)cyclopent-2-en-1-one

The acid ketone (7.4 g.) from Example 69 is Fisher esterified with 300ml. of absolute ethanol and 400 mg. of p-toluenesulfonic acid for 18hours, cooled, and the solvent is evaporated. The resulting oil isdissolved in ether, washed with dilute sodium bicarbonate solution, andsaline, dried (MgSO₄), and evaporated to give 7.306 g. (86%) of a lightyellow oil.

EXAMPLE 71 Preparation of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(7-p-tolenesulfonyloxy)-2-cyclopentene(Example 18) with sodium cyanide in the manner of Example 50 isproductive of the subject compound.

EXAMPLE 72 Preparation of2-(7-carboxyheptyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene(Example 71) by the procedure of Example 51 is productive of the subjectcompound.

EXAMPLE 73 Preparation of 2-(7-carboxyheptyl)-2-cyclopenten-1-one

Hydrolysis of the methoxime of Example 72 with acetone-hydrochloric acidby the procedure of Example 52 is productive of the subject compound.

EXAMPLE 74 Preparation of 2-(7-carbethoxyheptyl)-2-cyclopenten-1-one

Fisher estification of the carboxylic acid of Example 73 by theprocedure of Example 53 is productive of the subject compound.

EXAMPLE 75 Preparation of2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene(Example 60) with sodio diethyl phenylmalonate by the procedure ofExample 61 is productive of the subject compound

EXAMPLE 76 Preparation of2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example75) by the procedure of Example 20 is productive of the subject diacid.

EXAMPLE 77 Preparation of2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Decarboxylation of2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example76) by the procedure of Example 63 is productive of the subjectcompound.

EXAMPLE 78 Preparation of2-(6-carboxy-6-phenylhexyl)-2-cyclopentene-1-one

Methoxime cleavage of2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 77) inthe manner of Example 69 is productive of the subject ketone.

EXAMPLE 79 Preparation of2-(6-carbethoxy-6-phenylhexyl)-2-cyclopenten-1-one

Fisher esterification of the carboxylic acid of Example 78 in the mannerof Example 70 is productive of the subject keto-ester.

EXAMPLE 80 Preparation of2-(6-fluoro-6,6-dicarbethocyhexyl)-1-methoximino-2-cyclopentene

An ethanolic solution of sodium ethoxide, prepared from 0.389 g. ofsodium and 40 ml. of absolute ethanol, is treated at ambienttemperatures with 5.05 g. of2-(6,6-dicarbethoxyhexyl)-1-methoximino-2-cyclopentene (Example 61). Theresulting solution is cooled to -20° C. and then treated with a streamof perchloryl fluoride until the mixture becomes neutral. The excessperchloryl fluoride is removed with a stream of nitrogen and the mixtureis retreated with 10 ml. of an ethanolic solution of sodium ethoxide(from 0.350 g. of sodium) and then with perchloryl fluoride until themixture becomes neutral. The excess perchloryl fluoride is removed witha stream of nitrogen and the mixture is filtered and evaporated to anoil. The latter is partitioned between ether and water and the organicphase is washed with saturated saline, dried (Na₂ SO₄) and evaporated toafford the subject compound.

EXAMPLE 81 Preparation of 2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-one

A solution of 50 g. of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli etal., Tetrahedron Letters, No. 5, 465 (1966)]in 1400 ml. of n-butanolcontaining 2.7 g. of p-toluenesulfonic acid monohydrate is allowed tostand at room temperature in a stoppered flask for about 24 hours. Thesolution is taken to dryness. The residue is taken up in ether and theethereal solution is washed several times with saline solution, driedwith anhydrous magnesium sulfate, and taken to dryness to afford thesubject butyl ester.

EXAMPLES 82-84

Treatment of 2-(6-carboxyhexyl)cyclopent-2-en-1-one by the procedure ofExample 81 with the appropriate alcohol affords the esters of thefollowing table.

                  TABLE IV                                                        ______________________________________                                        Example Alcohol   Product Ester                                               ______________________________________                                        82      isopropanol                                                                             2-(6-carboisopropoxyhexyl)cyclopent-2-                                        en-1-one                                                    83      methanol  2-(6-carbomethoxyhexyl)cyclopent-2-en-                                        1-one                                                       84      1-hydroxy-                                                                              2-(6-carbo-n-decyloxyhexyl)cyclopent-2-                             n-decane  en-1-one                                                    ______________________________________                                    

EXAMPLE 85 Preparation of diethyl (5-chloro-1,1-dimethylpentyl)malonate

To magnesium (71 g. 2.92 moles) under 1 l. of ether containing a fewcrystals of iodine is added dropwise 1-chloro-4-bromobutane (500 g.,2.92 moles) over a period of 30 minutes with stirring under nitrogen.The reaction is maintained at a temperature of 0° C. to 5° C. byimmersing in an acetone-Dry Ice bath periodically. After stirring for 30minutes at room temperature, the solution is chilled to below 0° C. andis then transferred to a dropping funnel from which it is added dropwiseto diethyl isopropylidene malonate (440 g. 2.19 moles) [A. C. Cope andE. M. Hancock, J.A.C.S. 60, 2644 (1938)] dissolved in 1000 ml. of ethercontaining the tri(n-butyl)phosphine complex of copper (I) iodide (57g.) [G. B. Kaufman and L. A. Teter, Inorganic Synthesis, 7, 9(1963)] at-10° C. with stirring under nitrogen over a period of two hours. Afterstirring at room temperature for four hours, the reaction mixture ispoured into cold dilute hydrochloric acid and is extracted with ether.The combined ether extracts are washed with saline solution, dried overmagnesium sulfate, and concentrated in vacuo to give 700 g. of crudeamber oil, which is distilled under vacuum to yield two fractions: 212.4g. with b.p. at 110° C.-135° C. at 0.3 mm. and 100.0 g. with b.p. at135° C.-145° C. at 0.3 mm. The total yield is 312.4 g. (49%).

EXAMPLE 86 Preparation of 3,3-dimethyl-7-chloroheptanoic acid

A mixture containing diethyl 5-(5-chloro-1,1-dimethylpentyl)malonate(648 g., 2.22 moles) potassium hydroxide (460 g.) and eight liters of1:1 isopropanol:water is stirred at room temperature overnight. Most ofthe isopropanol is distilled and the residue is diluted with water, andthen carefully acidified with conc. hydrochloric acid. The mixture isextracted with ether and the extracts are washed with water and saline,dried over magnesium sulfate and concentrated in vacuo to give 548 g. ofcrude oil. The oil is dissolved in three liters of diglyne which isheated under reflux for sixteen hours. About 2.7 l. of solvent isdistilled, and the remainder is diluted with water and extracted withether. The extracts are washed with saline, dried over magnesium sulfateand concentrated in vacuo to give 428 g. of crude oil (99%).

EXAMPLE 87 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3,3-dimethyl-7-chloroheptanoic acid (428 g., 2.21moles) in 3 l. of chloroform containing 3 ml. of N,N-dimethylformamideis added 500 ml. of thionyl chloride and the resulting solution istested under reflux for three hours. The reaction solution then isconcentrated in vacuo and the residual acid chloride is dissolved in aminimum amount of benzene and added slowly to a solution containing 1260ml. of 95% ethanol and 2520 ml. of benzene and 390 ml. of collidine.After heating under reflux for one hour, the solution is concentratedand the residue is dissolved in ether washed with water, dilute sodiumbicarbonate solution and saline solution, dried over magnesium sulfateand concentrated to give 415 g. of crude oil, which is distilled undervacuum to yield two fractions: 46.6 g. boiling at 75° C. (0.3 mm.) and236.7 g. boiling at 75° C.-80° C. (0.3 mm). The total yield is 283.3 g.(60%) and the product is indicated to be 95% pure by g.l.c.

EXAMPLE 88 Preparation of methyl/ethyl2-(6-carbethoxy-5,5-dimethylhexyl) cyclopentanone-2-carboxylate

Sodium hydride (67 g., 1.55 moles) is placed in a three l. round-bottomflask and to this is added 1.1 liters of glyme from a dropping funnelunder nitrogen flow and with stirring. To the resulting grayish mixtureis added the 2-carbalkoxycyclopentanone (mixed methyl and ethyl esters)dropwise over a period of 45 minutes with nitrogen flow whilst thetemperature is maintained in the range of 40°-55°. Ethyl3,3-dimethyl-7-chloroheptanoate (283 g., 1.28 moles) and potassiumiodide (195 g., 1.32 moles) are added and the mixture is heated atreflux overnight. After most of the solvent is distilled, the residue ismade acidic with dilute hydrochloric acid and is then extracted withether. The ether extracts are washed with water and saline solution,dried over magnesium sulfate, and concentrated in vacuo to 500 g. ofcrude yellow oil, which is distilled to give 405 g. (94% yield) of oilwith b.p. 140°-180° (0.8 mm).

EXAMPLE 89 Preparation of 7-(2-Cyclopentanone)-3,3-dimethylheptanoicacid

Methyl/Ethyl2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentanone-2-carboxylate (200 g.,0.6 moles), glacial acetic acid (180 ml) and 240 ml. of dilutedhydrochloric acid, prepared from 100 ml. of conc. hydrochloric acid and300 ml. of water, are placed in a 2 l. flask, containing a refluxcondenser and a magnetic stirrer. The mixture then is stirred at refluxfor 24 hours. The reaction mixture is cooled, 1 l. of water is added andthe mixture is extracted several times with benzene. The organicextracts are combined, washed with saturated sodium chloride solution,dried over magnesium sulfate, filtered and concentrated to an oil (173.5g.). The oil is rendered basic with sodium hydroxide solution, extractedwith benzene and made acidic with hydrochloric acid and reextracted withbenzene several times. The benzene layers are combined and washed withwater, saturated sodium chloride solution, dried over magnesium sulfate,filtered and concentrated to yield 109.8 g. (78%) of crude oil, whichwas used without further purification in the next step.

EXAMPLE 90 Preparation of Ethyl7-(2-Cyclopentanone)-3,3-dimethylheptanoate

To a solution of 7-(2-cyclopentanone)-3,3-dimethylheptanoic acid (45 g.,0.22 mol.) in 285 ml. of chloroform containing three drops ofN,N-dimethylformamide is added dropwise 25 ml. of thionyl chloride. Thesolution is stirred at room temperature for twenty minutes, the solventis removed at reduced pressure and the residual acid chloride isdissolved in a minimum amount of benzene and added slowly to a solutioncontaining 115 ml. of ethanol, 230 ml. benzene and 30 ml. of collodine.This solution is heated under reflux for fifteen minutes and thenconcentrated. The residue is dissolved in ether, washed with water,diluted sodium bicarbonate solution and saline solution, dried overmagnesium sulfate and concentrated to give 51 g. of crude oil.Distillation gives 40 g. (67%) b.p. 135-145 (0.1 mm.) of oil.

EXAMPLE 91 Preparation of1-Acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene

A solution of ethyl 7-(2-cyclopentanone)-3,3-dimethylheptanoate (90 g.,0.336 mol.) and p-toluenesulfonic acid (0.94 g.) in 250 ml. of aceticanhydride is heated to boiling under partial reflux, allowing distillateat 118° or less (i.e. acetic acid) to escape thru a Vigreux columnequipped with a condenser to collect the distillate. After ten hours 130ml. of distillate is collected. Another 50 ml. of acetic anhydride isadded and the reaction is heated for five more hours; an additional 125ml. of acetic anhydride is added, the reaction is heated for seven morehours; finally another 50 ml. of acetic anhydride is added and heatingis continued for four more hours. The solution is cooled and poured(cautiously) into a cold (0°-5°) mixture of saturated aqueous sodiumbicarbonate (400 ml.) and hexane (250 ml.). The resulting cold mixtureis stirred for thirty minutes during which time portions of solid sodiumbicarbonate are added periodically until carbon dioxide evalutionceases. The hexane layer is separated and washed with saturated sodiumchloride solution until the washings are neutral, dried over magnesiumsulfate and treated with Darco decolorizing charcoal for clarificationand then evaporated to dryness leaving an amber colored oil (87.5 g.,84%).

EXAMPLE 92 Preparation of2-(6-Carboxy-5,5-dimethylhexyl)cyclopent-2-en-1 -one

To a rapidly stirred mixture of1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cycopent-1-ene (35 g., 0.113mole) chloroform (95 ml.), water (125 ml.) and calcium carbonate (11.8g.) cooled in an ice-bath is added dropwise over a period of thirtyminutes a solution of bromine (18.8 g.) in carbon tetrachloride (31ml.). After stirring in the cold for an additional 45 minutes the orangecolored chloroform layer is separated and washed with dilute sodiumbisulfite and saturated saline solution, dried over magnesium sulfateand taken to dryness in vacuo (bath temperature: 35°-40°) leaving anamber colored oil. A slurry of 100 ml. of N,N-dimethylacetamide and 16.5g. of CaCO₃ is stirred and heated to reflux under nitrogen flow. Theabove dried oil is added from a dropping funnel rapidly, maintainingreflux and nitrogen flow for thirty minutes. The cooled reaction mixtureis filtered, and the precipitate is washed with ether. The filtrate ispoured into two liters ice-cold water and is extracted with ether. Thecombined extracts and washing is washed with water, saturated saline,treated with decolorizing charcoal, filtered. The solvent evaporated invacuo to give 24 g. (77%) of subject product.

EXAMPLE 93 Preparation of 4-bromo-2(6-carboxyhexyl)cyclopent-2-en-1-one

A stirred mixture of 35.9 g. (0.171 moles) of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465(1966)], 35.0 g. (0.197 moles) of N-bromosuccinimide, and 600 ml. ofcarbon tetrachloride is refluxed for 35 minutes. The mixture is cooledto 5° C. and filtered. The filtrate is washed with cold water, driedover magnesium sulfate, and taken to dryness to give an oil,λ_(max).^(MeOH) =225 mμ (8850); νmax.=1705 (carbonyl groups) and 1625.cm⁻¹ (olefin group).

EXAMPLE 94 Preparation of2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one

To a stirred solution of 10.6 g. (ca. 34 moles) of crude4-bromo-2-(6-carboxyhexyl)cyclopent-2-en-1 -one (Example 93) in 100 ml.of acetone and 65 ml. of water is added 8.80 g. (45.2 mmoles) of silverfluoborate during 2 minutes. The temperature is maintained at 25°-30° C.by external cooling. The mixture is stirred for 90 minutes, filtered,saturated with sodium chloride, and extracted with ether. The extract isextracted with half saturated sodium bicarbonate solutions. The basicsolutions is reacidified with dilute hydrochloric acid, saturated withsodium chloride, and extracted with ether. The extract is washed withwater and saturated sodium chloride solution, dried over magnesiumsulfate, and concentrated. The crude product is purified by partitionchromatography on Celite to give an oil; λ_(max).^(MeOH) =233 mμ.(7360); νmax.=3380 (hydroxyl groups), 1710 (carbonyl groups), and 1632cm⁻¹ (olefin group).

EXAMPLE 95 Preparation of4-tetrahydropyranyloxy-2-(6-tetrahydropyranylcarboxyhexyl)cyclopent-2-en-1-one

To a stirred solution of 5.59 g. (24.6 mmoles) of4-hydroxy-2-(6-carboxyhexyl) cyclopent-2-en-1-one (Example 94) and 20.7g. (246 mmoles) of dihydropyran in 100 ml. of methylene chloride at 20°C. is added 47 mg. (0.246 mmoles) of p-toluenesulfonic acid monohydratein one portion. The temperature is maintained at 20°-25° C. by coolingand is stirred for one hour at that temperature. The solution is dilutedwith 200 ml. of ether and poured into a mixture of 40 ml. of saturatedsodium bicarbonate solution, 40 ml. of saturated sodium chloridesolution, and 80 ml. of water. The phases are separated, and the aqueousphase is extracted with additional ether. The total extract is washedsuccessively with water and saturated sodium chloride solution, driedover potassium carbonate, and freed of volatile matter by concentrationat reduced pressure to give an oil, λ_(max).^(MeOH) =223 mμ (9500);νmax. 1730 (ester carbonyl group), 1705 (ketone carbonyl group), and1030 cm⁻¹ (tetrahydropyranyloxy groups).

EXAMPLE 96 Preparation of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenonemethoxime

The subject compound is prepared from sodio diethyl methylmalonate and2-(5-methanesulfonyloxypentyl)-2-cyclopentenone methoxime (Example 60)by the procedure described in Example 61.

EXAMPLE 97 Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime

Saponification of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenone methoxime(Example 96) with potassium hydroxide by the method of Example 20 isproductive of 2-(6,6-dicarboxyheptyl)-2-cyclopentenone methoxime,decarboxylation of which in the manner of Example 63 provides thesubject compound.

EXAMPLE 98

Methoxime cleavage of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime(Example 97) in the manner of Example 22 provides the subject ketone.

EXAMPLE 99 Preparation of 2-(6-carbethoxyheptyl)-2-cyclopentenone

Esterification with ethanol of the acid chloride derived from2-(6-carboxyheptyl)-2-cyclopentenone in the manner of Example 31 isproductive of the subject compound.

EXAMPLE 100 Preparation of ethyl (methyl)7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate

To a stirred suspension of 51 g. of sodium hydride (57% in mineral oil)in 675 ml. of dimethylformamide is added 200 g. of 2-cyclohexanonecarboxylate (60% ethyl - 40% methyl esters) over a 1-5 hr. period withexternal cooling to maintain the temperature at 20°-25° C. The reactionmixture is stirred at ambient temperature for 15 minutes and heated to50° C. over 15 minutes. To the stirred mixture is added 300 g. of ethyl7-bromoheptanoate during a 10 minute period. The reaction mixture isstirred at 50°-60° C. for 4 hours, cooled, and poured into water. Theproduct is obtained by ether extraction. The extract is washedsuccessively with water and saturated sodium chloride, dried andevaporated to give a liquid which is purified by distillation, IR 1735cm⁻¹ (ester carbonyls) and 1710 cm⁻¹ (ketone carbonyl).

EXAMPLE 101 Preparation of 7 -(cyclohexan-1-on-2-yl)heptanoic acid

A stirred mixture of 380 g. of mixed methyl and ethyl esters of7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate (Example 10), 202 ml. ofconcentrated sulfuric acid, 970 ml. of glacial acetic acid, and 970 ml.of water if refluxed for 22.5 hours. The cooled reaction mixture istreated with 380 g. of sodium carbonate and 2 liters of water and isextracted with ether. Acidic material is partitioned from the etherextract with 1.0 M sodium carbonate. The aqueous phase is acidified withconcentrated hydrochloric acid and extracted with ether. The extract iswashed sucessively with water and saturated sodium chloride, dried, andevaporated to give an oil.

EXAMPLE 102 Preparation of ethyl 7-(cyclohexan-1-on-2-yl)heptanoate

A solution of 232 g. of 7-(cyclohexan-1-on-2-yl)heptanoic acid in 2500ml. of ethanol is refluxed for 4.5 hours with 3.8 g. ofp-toluenesulfonic acid monohydrate. The solution is diluted with 200 ml.of benzene, and boiling is continued for 2 hours as 200 ml. ofdistillate is removed. The volume of the solution is concentrated to 500ml. After dilution with 500 ml. of ether the solution is extracted witha solution prepared from 50 ml. of saturated sodium bicarbonate, 50 ml.of saturated sodium chloride, and 100 ml. of water. The extract iswashed with saturated sodium chloride, dried, and evaporated. Theproduct is purified by distillation to give a liquid, IR 1740 cm⁻¹(ester carbonyl) and 1715 cm⁻¹ (ketone carbonyl).

EXAMPLE 103 Preparation of2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)-cyclohexan-1-one

The subject compound is prepared in the manner described in Example 10by treatment of 2-cyclohexanone carboxylate (mixed methyl and ethylesters) with sodium hydride and ethyl 4-iodobutyrate.

EXAMPLE 104 Preparation of 2-(3-carbethoxypropyl)cyclohexan-1-one

This compound is prepared from2-carbalkoxy(methyl/-ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one(Example 13) by decarbalkoxylation according to the procedure describedin Example 11 followed by esterification by the procedure of Example 12.

EXAMPLE 105 Preparation of 2-(5-carbethoxypentyl)cyclohexan-1-one

This compound is prepared by alkylation of 2-cyclohexanone carboxylate(mixed methyl and ethyl esters) with ethyl 6-bromohexanoate according tothe procedure of Example 10, followed by decarbalkoxylation according tothe procedure of Example 11 and finally esterification by the procedureof Example 12.

EXAMPLE 106 Preparation of 2-(7-carbethoxyheptyl)cyclohexan-1-one

Alkylation of 2-cyclohexanone carboxylate (mixed methyl and ethylesters) with ethyl 8-bromoctanoate in accordance with the procedure ofExample 10, followed by decarbalkoxylation by the procedure of Example11 and then esterification by the procedure of Example 12 is productiveof the subject compound.

EXAMPLE 107 Preparation of ethyl7-(1-acetoxycyclohex-1-en-2-yl)heptanoate

A stirred solution of 28.0 g. of ethyl7-(cyclohexan-1-on-2-yl)heptanoate (Example 12), 170 mg. ofp-toluenesulfonic acid monohydrate, and 25.6 g. of acetic anhydride isheated for 5 hours while allowing 8.0 g. of distillate to distill. Thecooled solution is poured into a stirred, ice-cold mixture of 500 ml. ofsaturated sodium bicarbonate and 250 ml. of hexane. After one hour thehexane phase is separated dried, and evaporated. The crude product isdistilled to give a liquid, IR 1760 cm⁻¹ (vinyl ester carbonyl) and 1740cm⁻¹ (ethyl ester carbonyl).

EXAMPLE 108 Preparation of1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene

Treatment of (2-(3-carbethoxypropyl)cyclohexan-1-one (Example 14) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 109 Preparation of1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene

Treatment of 2-(5-carbethoxypentyl)cyclohexan-1-one (Example 15) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 110 Preparation of1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene

Treatment of 2-(7-carbethoxyheptyl)cyclohexan-1-one (Example 16) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 111 Preparation of ethyl 7-cyclohex-2-en-1-one-2-yl)heptanoate

To a stirred solution of ethyl 7-(1-acetoxycyclohex-1-en-2-yl)heptanoate(Example 24) in 750 ml. of acetic acid and 125 ml. of pyridine at 10° C.is added a solution of 13.8 g. of bromine in 200 ml. of acetic acid over20 minutes. The resulting solution is allowed to stand at ambienttemperature for 45 minutes and is then decolorized with sodium sulfite.The solution is poured into 800 ml. of half-saturated sodium chlorideand extracted with 1:1 hexane-ether. The extract is washed successivelywith water and saturated sodium chloride, dried over sodium carbonate,and evaporated to give 32 g. of the crude bromoketone. To a stirredsuspension of 14.2 g. of lithium bromide and 16.6 g. of lithiumcarbonate in 250 ml. of anhydrous dimethylformamide at 80° C. is addedthe above bromoketone. The stirred mixture is heated to boiling over 20minutes and refluxed for 15 minutes. The cooled mixture is poured into1000 ml. of water, acidified with dilute hydrochloric acid, andextracted with ether. The extract is washed successively with water andsaturated sodium chloride, dried, and evaporated. The product ispurified by distillation to give a liquid, IR 1740 cm⁻¹ (estercarbonyl), 1685 cm⁻¹ (ketone carbonyl), and 1650 cm⁻¹ (olefin); NMR(CCl₄) 6.63 (multiplet, vinyl proton).

EXAMPLE 112 Preparation of 2-(3-carbethoxypropyl)cyclohex-2-en-1-one

In accordance with the procedure of Example 40, bromination of1-acetoxy-2-(3-carbethoxypropyl)cyclohexyl-1-ene (Example 25) followedby treatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 113 Preparation of 2-(5-carbethoxypentyl)cyclohex-2-en-1-one

By the product of Example 40, bromination of1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene (Example 26) followed bytreatment with lithium bromide and lithium carbonate is productive o thesubject compound.

EXAMPLE 114 Preparation of 2-(7-carbethoxyheptyl)cyclohex-1-en-2-one

By the procedure of Example 40, bromination of1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene (Example 27) followed bytreatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 115 Preparation of2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene

In the manner described in Example 34, treatment of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene with p-toluene sulfonylchloride in pyridine gives the subject product as a light yellow oil; IR(film): 1600, 1190, 1050, 885 cm⁻¹.

EXAMPLE 116 Preparation of2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene

To a stirred mixture of 1.465 g. (0.0348 mole) of sodium hydride (57.2%in mineral oil) in 50 ml. of dimethoxyethane, under nitrogen, is addedslowly 4.8 g. (0.0347 mole) of ethyl-2-mercaptoacetate. The reactionmixture is stirred at room temperature for one hour and then a solutionof 7.8 g. (0.0231 mole of2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene in 30 ml.of dimethoxyethane is added dropwise and stirred at room temperature for18 hours. The solution is heated at reflux for one hour, cooled andpoured into cold dilute hydrochloric acid and then extracted with ether.The combined ether extracts are washed with saline, dried over magnesiumsulfate and evaporated to give 7.6 g. of subject product as a yellowoil.

EXAMPLE 117 Preparation of 2-(6-carboxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 38, treatment of2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene with acetoneand 2N hydrochloric acid at reflux gives the subject product as a yellowoil.

EXAMPLE 118 Preparation of 2-(6-carbethoxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 39, treatment of2-(6-carboxy-5-thiahexyl)-2-cyclopentenone with p-toluenesulfonic acidin ethanol gives the subject ester as a yellow oil.

EXAMPLE 119 Preparation of 3-triphenylmethoxy-1-octyne

A mixture of 1.26 g. (10.0 mmoles) of 1-octyn-3-ol, 4.85 g. (15.0mmoles) of triphenylmethyl bromide, and 50 ml. of dry pyridine is heatedat 95° C. for 60 minutes with occasional swirling. The solution iscooled, treated with water, and extracted with ether. The extract iswashed successively with water and saturated sodium chloride solution,dried over magnesium sulfate, and concentrated. The crude product ispurified by chromatography on Florisil and recrystallization frompetroleum ether to give white crystals, m.p. 65°-66.5°, ν_(max). (KBr)3280 (acetylenic hydrogen), 1605, 1030, and 702 cm⁻¹ (triphenylmethoxygroup).

EXAMPLE 120 Preparation of ethyl9-oxo-15-triphenylmethoxy-13-trans-8ξ-prostenoate

A stirred solution of 7.37 g. (20.0 mmoles) of3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. of benzene istreated with 16.7 mg. of 1.2 M diisobutylaluminum hydride in hexane, andthe resulting solution is heated at 50° C. for 2 hours. The solution iscooled to 0° C. and treated with 10.5 ml. of 1.7 M methyl lithium inether. After stirring for a 20 minute period at ambient temperature, thealanate solution is cooled to 0° C. and treated with a solution of 3.98g. (16.7 mmoles) of 2-(6-cabethoxyhexyl)cyclopent-2-en-1-one (Example13) in 5 ml. of ether. The resulting solution is stirred at ambienttemperature for 22.5 hours, diluted with ether, and poured into astirred mixture 2N acetic acid and ice. After stirring until methaneevolution ceases, the organic phase is separated and washed successivelywith water and saturated sodium chloride solution. The extract is driedover magnesium sulfate and concentrated. The crude product in theresidue is purified by chromatography on silica gel to give an oil,νmax. 1735 (carbonyl groups), 967 (trans vinyl group), and 705 cm⁻¹(triphenylmethoxy group).

EXAMPLE 121 Preparation of ethyl 15-hydroxy-9-oxo-13-trans-prostenoate

A 0.05M solution of ethyl9-oxo-15-triphenylmethoxy-13-trans-8ξ-prostenoate (Example 120) inglacial acetic acid-tetrahydrofuran-water (4:2:1) is heated at 45° C.for 3.5 hours. The solvents are evaporated at reduced pressure, and theresidue is dissolved in ether. The solution is washed successively withwater, 0.5M sodium bicarbonate solution, and saturated sodium chloridesolution; dried over magnesium sulfate; and concentrated. Columnchromatography of the crude product on silica gel gives two epimericsubstances which are purified separately by thin lyer chromatography togive oils differing only in chromatographic behavior, νmax. 3470(hydroxyl group), 1735 (carbonyl groups), and 967 cm⁻¹ (trans vinylgroup).

EXAMPLE 122 Preparation of 15-hydroxy-9-oxo-13-trans-prostenoic acid

A solution of 2 g. of ethyl 15-hydroxy-9-oxo-13,14-trans-prostenoate(Example 121) (mixture of racemates) in 32 ml. of methanol-water (1:1),containing 850 mg. of potassium hydroxide is stirred at ambienttemperature for 18 hours. After acidification with 10% hydrochloricacid, the solution is extracted with ether several times. The combinedether extracts are washed with saturated sodium chloride solution, driedwith anhydrous magnesium sulfate and taken to dryness to give 1.69 g.(92%) of an oil which partially crystallizes. Recrystallized fromether-hexane gives white crystals, m.p. 79°-81° C.; nmr δ 6.36 (s,hydroxyl and carboxyl groups), 5.61 (t, olefinic protons), 4.12 (s, C₁₈-H) and 0.90 (s, terminal methyl).

EXAMPLE 123 Preparation of tetrahydropyran-2-yl-9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-8ξ-prostenoate

In the manner described in Example 120, 13.6 g. (37 mmoles) of3-triphenylmethoxy-1-octyne (Example 119) contained in 18.5 ml. ofbenzene is converted to an alanate reagent by treatment with 31 ml. of1-2N diisobutylaluminum hydride in hexane and 21 ml. of 1.7M methyllithium in ether. To the stirred, ice-cold reagent is added a solutionof 10.97 g. (24.6 mmoles) of2-(6-tetrahydropyranylcarboxyhexyl)-4-tetrahydropyranyloxycyclopent-2-en-1-one(Example 95) in 10 ml. of ether during 10 minutes. The resultingsolution is stirred at ambient temperature for 20 hours, diluted withether, and poured into a stirred mixture of 2N hydrochloric acid andice. The organic phase is separated and washed successively with waterand saturated sodium chloride solution. The extract is dried overmagnesium sulfate, and the solvents are evaporated at reduced pressureto give the crude product as an oil, νmax. 1735 (carbonyl groups), 1030(tetrahydropyranyloxy groups), 970 (trans vinyl group), and 705 cm⁻¹(triphenylmethoxy group).

EXAMPLE 124 Preparation of 11,15-dihydroxy-9-oxo-13-trans-prostenoicacids

A 0.05M solution of crude tetrahydropyran-2-yl9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-prostenoate(Example 123) in glacial acetic acid-tetrahydrofuran-water (4:2:1) isheated at 45° C. for 3.5 hours. The solution is diluted with water andextracted with ether. The extract is washed successively with water andsaturated sodium chloride solution and dried over magnesium sulfate. Thesolvents are removed at reduced pressure. Column chromatography of theresidue on acid-washed silica gel gives the title compounds as a pair ofepimeric substances which are purified separately by partitionchromatography.

The fast-running epimer (15-epi-d,l-prostaglandin E₁) is obtained as anoil, νmax. 1735 (ketone carbonyl group), 1710 (acid carbonyl group), and967 cm⁻¹ (trans vinyl group); NMR (acetone-d₆) 5.68 (multiplet, vinylhydrogens) and 4.11 Ε(multiplet, carbinolic hydrogens).

The slow-running epimer (d,l-prostaglandin E₁) is recrystallized fromethyl acetate-petroleum ether to give white crystals, m.p. 100°-105° C.,νmax. (KBr) 1725 (ketone carbonyl group), 1700 (acid carbonyl group),and 970 cm⁻¹ (trans vinyl group); NMR (acetone-d₆) 5.67 (multiplet,vinyl hydrogens) and 4.12 (multiplet, carbinolic hydrogens).

EXAMPLES 125 to 139

In accordance with the method described in Example 119, the various3-hydroxy-1-alkynes listed in the table below are converted to thecorresponding 3-triphenylmethoxy-1-alkynes by treatment withtriphenylmethyl bromide.

                  TABLE                                                           ______________________________________                                        125  1-heptyn-3-ol   3-triphenylmethoxyheptyne-1                              126  1-hexyn-3-ol    3-triphenylmethoxy-hexyne-1                              127  1-pentyn-3-ol   3-triphenylmethoxy-pentyne-1                             128  1-nonyne-3-ol.sup.a                                                                           3-triphenylmethoxy-nonyne-1                              129  2-decyne-3-ol.sup.b                                                                           3-triphenylmethoxy-decyne-1                              130  4-ethyl-1-octyne-3-ol                                                                         3-triphenylmethoxy-4-ethyl-                                                   octyne-1                                                 131  4-ethyl-1-hexyne-3-ol                                                                         3-triphenylmethoxy-4-ethyl-                                                   hexyne-1                                                 132  4-methyl-1-heptyne-3-ol                                                                       3-triphenylmethoxy-4-methyl-                                                  heptyne-1                                                133  4-methyl-1-pentyne-3-ol                                                                       3-triphenylmethoxy-4-methyl-                                                  pentyne-1                                                134  7-methyl-6-en-1-octyne-                                                                       3-triphenylmethoxy-7-methyl-                                  3-ol.sup.c      6-en-octyne-1                                            135  6,7-dimethyl-6-en-1-                                                                          3-triphenylmethoxy-6,7-                                       octyn-3-ol.sup.c                                                                              dimethyl-6-en-octyne-1                                   136  7-isobutyl-6-en-1-                                                                            3-triphenylmethoxy-7-isobutyl-                                octyne-3-ol.sup.c                                                                             6-en-octyne-1                                            137  5-en-1-hexyne-3-0l.sup.d                                                                      3-triphenylmethoxy-5-en-                                                      hexyne-1                                                 138  5,9-dimethyl-9-en-1-                                                                          3-triphenylmethoxy-5,9-                                       decyne-3-ol.sup.e                                                                             dimethyl-9-en-decyne-1                                   139  cis-5-en-1-octyne-3-                                                                          3-triphenylmethoxy-cis-5-en-                                  ol.sup.f        octyne-1                                                 ______________________________________                                         References:                                                                   .sup.a M. Bertrand, Bull. Soc. Chim. France, 461 (1956).                      .sup.b F. Bohlmann and D. Rats, Chem. Ber., 90, 2265 (1957).                  .sup.c U.S. Pat. No. 3,452,105 (June 24, 1969); Chem. Abs., 71, 60678         (1969).                                                                       .sup.d A. Viola and J. H. MacMillan, Jour. Amer. Chem. Soc., 92, 2404         (1970).                                                                       .sup.e Sequin, Bull. Soc. Chim. France, 12, 948 (1945).                       .sup.f J. Fried et al., Jour. Amer. Chem. Soc., 94, 4342 (1972).         

EXAMPLES 140-256

Treatment of the cycloalkenone designated in the table below with thealanate [lithiumdiisobutyl-methyl-(3-triphenylmeythoxy-1-trans-alkenyl)-alanate]prepared by treatment of the listed -3-triphenylmethoxy-1-alkyne withdiisobutyl aluminum hydride followed with methyl lithium, all by theprocedure described in Example 120, is productive9-oxo-15-triphenylmethoxy-13-trans-8-ξ-prostenoates of the table.

                                      Table 3                                     __________________________________________________________________________                     Starting 3-triphenyl-                                                                      Product                                              Starting Cycloalkenone                                                                    methoxy-1-alkyne of                                                                     Alkyl 9-oxo-15-triphenylmethoxy-13-trans-          Example                                                                            of Example  Example   8ξ -prostenoate                                 __________________________________________________________________________    140  14          119       ethyl 9-oxo-15-triphenylmethoxy-5,6,7-tri-                                    nor-13-trans-8ξ -prostenoate                    141  23          119       ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bis-                                    homo-13-trans-8ξ -prostenoate                   142  31          119       ethyl-9-oxo-15-triphenylmethoxy-2-ethyl-13-                                   trans-8ξ -prostenoate                           143  41          119       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 13-trans-8ξ -prostenoate                        144  46          119       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-13-                                     trans-8ξ -prostenoate                           145  53          119       ethyl 9-oxo-15-triphenylmethoxy-7-nor-13-                                     trans-8ξ -prostenoate                           146  70          119       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-13-                                  trans-8ξ -prostenoate                           147  74          119       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-13-                                   13-trans-8ξ -prostenoate                        148  79          119       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-13-                                  trans-8ξ -prostenoate                           149  99          119       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-13-                                  trans-8ξ -prostenoate                           150  111         119       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-13-                                  trans-8ξ -prostenoate                           151  112         119       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,-                                  6,7-trinor-13-trans-[ξ -prostenoate             152  113         119       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7-                                   nor-13-trans-8ξ -prostenoate                    153  114         119       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-13-trans-8ξ -prostenoate                   154  118         119       ethyl 9-oxo-15-triphenylmethoxy-3-thia-13-                                    13-trans-8ξ -prostenoate                        155  81          119       butyl 9-oxo-15-triphenylmethoxy-13-trans-8ξ                                -   prostenoate                                    156  82          119       isopropyl 9-oxo-15-triphenylmethoxy-13-trans-                                 8ξ -prostenoate                                 157  83          119       methyl 9-oxo-15-triphenylmethoxy-13-trans-8ξ                                -                                                                            prostenoate                                        158  84          119       n-decyl 9-oxo-15-triphenylmethoxy-13-trans-                                   8ξ -prostenoate                                 159  900         119       methyl 9-oxo-15-triphenylmethoxy-5-cis,13-                                    trans-8ξ -prostadienoate                        160  13          125       ethyl 9-oxo-15-triphenylmethoxy-20-nor-13-                                    trans-8ξ -prostenoate                           161  13          128       ethyl 9-oxo-15-triphenylmethoxy-20-methyl-                                    13-trans-8ξ -prostenoate                        162  13          130       ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-13-                                  trans-8ξ -prostenoate                           163  13          132       ethyl 9-oxo-15-triphenylmethoxy-16-methyl-20-                                 nor-13-trans-[ξ -prostenoate                    164  13          134       ethyl 9-oxo-15-triphenylmethoxy-19-methyl-13-                                 trans-18,8ξ -prostadienoate                     165  13          135       ethyl 9-oxo-15-triphenylmethoxy-18,19-di-                                     methyl-13-trans,18-8ξ -prostadienoate           166  13          139       ethyl 9-oxo-15-triphenylmethoxy-8ξ                                         -13-trans,                                                                    17-cis-prostadienoate                              167  14          139       ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trinor-                                 8ξ -13-trans,17-cis-prostadienoate              168  15          139       ethyl 9-oxo-15-triphenylmethoxy-6,7-dinor-8ξ                                -                                                                            13-trans,17-cis-prostadienoate                     169  23          139       ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bishomo-                                4                                                                             8ξ -13-trans,17-cis-prostadienoate              170  31          139       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-8ξ                                 -13-                                                                          trans,17-cis-prostadienoate                        171  41          139       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 8ξ -13-trans,17-cis-prostadienoate              172  46          139       ethyl 9-oxo-15-triphenylmethoxy-3-oxo-8ξ                                   -13-                                                                          trans,17-cis-prostadienoate                        173  53          139       ethyl 9-oxo-15-triphenylmethoxy-7-nor-8ξ                                   -13-                                                                          trans,17-cis-prostadienoate                        174  70          139       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-8ξ                                -13-                                                                          trans,17-cis-prostadienoate                        175  74          139       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-8ξ                                 -13-                                                                          trans,17-cis-prostadienoate                        176  79          139       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-8ξ                                -13-                                                                          trans,17-cis-prostadienoate                        177  99          139       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-8ξ                                -13-                                                                          trans,17-cis-prostadienoate                        178  111         139       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-8ξ                                -13-                                                                          trans,17-cis-prostadienoate                        179  112         139       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6,7-                               O                                                                             trinor-13-trans, 17-cis-prostadienoate             180  113         139       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7-nor-                               N                                                                             8ξ -13-trans,17-cis-prostadienoate              181  114         139       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bishomo-                               O                                                                             8ξ -13-trans,17-cis-prostadienoate              182  118         139       ethyl 9-oxo-15-triphenylmethoxy-3-thia-8ξ                                  -13-                                                                          trans,17-cis-prostadienoate                        183  81          139       butyl 9-oxo-15-triphenylmethoxy-8ξ                                         -13-trans,17-                                                                 cis-prostadienoate                                 184  82          139       isopropyl 9-oxo-15-triphenylmethoxy-8ξ                                     -13-trans,                                                                    cis-prostadienoate                                 185  83          139       methyl 9-oxo-15-triphenylmethoxy-8ξ                                        -13-trans,                                                                    17-cis-prostadienoate                              186  84          139       n-decyl 9-oxo-15-triphenylmethoxy-8ξ                                       -13-trans,17-                                                                 cis-prostadienoate                                 187  14          136       ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trinor-19                               -                                                                             isobutyl-8ξ -13-trans,18-prostadienoate         188  14          137       ethyl 9-oxo-15-triphenylmethoxy-5,6,7,19,20-pen                               ta-                                                                           nor-8ξ -13-trans-17,prostadienoate              189  13          137       ethyl 9-oxo-15-triphenylmethoxy-19,20-dinor-8.x                               i. -13-                                                                       trans,18-prostadienoate                            190  13          138       ethyl 9-oxo-15-triphenylmethoxy-17-methyl-20-is                               o-                                                                            propenyl-8ξ -trans-prostenoate                  191  15          131       ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-6,7,19                               ,                                                                             20-tetranor-8ξ -13-trans-prostenoate            192  15          135       ethyl 9-oxo-15-triphenylmethoxy-18,19-dimethyl-                               6,                                                                            7-dinor-8ξ -13-trans,18-prostadienate           193  23          130       ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-7a,7b-                               2                                                                             bishomo-8ξ -13-trans-prostenoate                194  23          134       ethyl 9-oxo-15-triphenylmethoxy-19-methyl-7a,7b                               -                                                                             bishomo-8ξ -13-trans,18-prostadienoate          195  31          126       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-19,20-                                O                                                                             dinor-8ξ -13-trans-prostenoate                  196  31          129       ethyl 9-oxo-15-triphenylmethoxy-2,20-diethyl-                                 8ξ -13-trans-prostenoate                        197  31          132       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-16-                                   methyl-8ξ 20-nor-13-trans-prostenoate           198  31          135       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-18,                                   19-dimethyl-8ξ -13-trans,18-prostadienoate      199  41          127       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 18,19,20-trinor-8ξ -13-trans-prostenoate        200  41          128       ethyl 9-oxo-15-triphenylmethoxy-3,3,20-tri-                                   methyl-8ξ -13-trans-prostenoate                 201  41          132       ethyl 9-oxo-15-triphenylmethoxy-3,3,16-tri-                                   methyl-20-nor-8ξ -13-trans-prostenoate          202  41          136       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 19-isobutyl-8ξ -13-trans,18-prostadienoate      203  41          137       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 19,20-dinor-8ξ -13-trans,17-prostadienoate      204  46          125       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-nor-                                 8ξ -13-trans-prostenoate                        205  46          128       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-                                     methyl-8ξ -13-trans-prostenoate                 206  46          130       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                     ethyl-8ξ-13-trans-prostenoate                   207  46          132       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                     methyl-20-nor-8ξ-13-trans-prostenoate           208  46          137       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-19,20-                                  dinor-8ξ-13-trans,17-prostadienoate             209  53          137       ethyl 9-oxo-15-triphenylmethoxy-7,19,20-tri                                   nor-8ξ-13-trans,17-prostadienoate               210  53          135       ethyl 9-oxo-15-triphenylmethoxy-7-nor-18,19-                                  dimethyl-8ξ-13-trans,18-prostadienoate          211  53          133       ethyl 9-oxo-15-triphenylmethoxy-7,18,19,20-                                   tetranor-16-methyl-8ξ-13-trans-prostenoate      212  70          125       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20-                                  nor-8ξ-13-trans-prostenoate                     213  70          129       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20-                                  ethyl-8ξ-13-trans-prostenoate                   214  70          131       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16-                                  ethyl-19,20-dinor-8ξ-13-trans-prostenoate       215  70          132       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16-                                  methyl-20-nor-8ξ-13-trans-prostenoate           216  70          134       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-19-                                  methyl-8ξ-13-trans,18-prostadienoate            217  74          135       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-18,19-                                N                                                                             dimethyl-8ξ-13-trans,18-prostadienoate          218  74          137       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-19,20-                                O                                                                             dinor-8ξ-13-trans,17-prostadienoate             219  79          125       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20-                                  nor-8ξ-13-trans-prostenoate                     220  79          129       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20-                                  ethyl-8ξ-13-trans-prostenoate                   221  79          130       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16-                                  ethyl-8ξ-13-trans-prostenoate                   222  79          133       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16-                                  methyl-18,19,20-trinor-8ξ-13-trans-prostenoa                               te                                                 223  79          135       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-18,                                  19,-dimethyl-8ξ-13-trans,18-prostadienoate      224  99          125       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-20-                                  nor-8ξ-13-trans-prostenoate                     225  99          128       ethyl 9-oxo-15-triphenylmethoxy-2,20-dimethyl-                                O                                                                             8ξ-13-trans-prostenoate                         226  99          131       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-16-                                  ethyl-19,20-dinor-8ξ-13-trans-prostenoate       227  99          134       ethyl 9-oxo-15-triphenylmethoxy-2,19-dimethyl-                                8ξ-13-trans,18-prostadienoate                   228  99          137       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-19,                                  20-dinor-8ξ-13-trans,17-prostadienoate          229  111         125       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20-       nor-8ξ-13-trans-prostenoate                                                230  111         128       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20-                                  methyl-8ξ-13-trans-prostenoate                  231  111         130       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-16-                                  ethyl-8ξ-13-trans-prostenoate                   232  111         135       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-18,                                  19-dimethyl-8ξ-13-trans,18-prostadienoate       233  111         137       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19,                                  20-dinor-8ξ-13-trans,17-prostadienoate          234  112         129       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6                                  7-trinor-20-ethyl-8ξ-13-trans-prostenoate       235  112         132       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6,                                 7,20-tetranor-18-methyl-8ξ-13-trans-prost-                                 enoate                                             236  112         136       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6,7-                               trinor-19-isobutyl-8ξ-13-trans,18-prostadien                               oate                                               237  113         128       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20-                                  methyl-8ξ-13-trans-prostenoate                  238  113         134       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19-                                  methyl-8ξ-13-trans,18-prostadienoate            239  114         125       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-20-nor-8ξ-13- trans-prostenoate            240  114         129       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-20-ethyl-8ξ-trans-prostenoate              241  114         132       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-16-methyl-20-nor-8ξ-13-trans-prostenoat                               e                                                  242  114         134       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-19-methyl-8ξ-13-trans,18-prostadienoate    243  118         125       ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-nor-                                8ξ-13-trans-prostenoate                         244  118         128       ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-methy                               l-                                                                            8ξ-13-trans-prostenoate                         245  118         130       ethyl 9-oxo-15-triphenylmethoxy-3-thia-16-ethyl                               -                                                                             8ξ-13-trans-prostenoate                         246  118         133       ethyl 9-oxo-15-triphenylmethoxy-3-thia-16-                                    methyl-18,19,20-trinor-8ξ-13-trans-prostenoa                               te                                                 247  118         134       ethyl 9-oxo-15-triphenylmethoxy-3-thia-19-methy                               l-                                                                            8ξ-trans,18-prostadienoate                      248  118         137       ethyl 9-oxo-15-triphenylmethoxy-3-thia-19,20-                                 dinor-8ξ-13-trans,17-prostadienoate             249  900         125       methyl 9-oxo-15-triphenylmethoxy-20-nor-8ξ-5                               -                                                                             cis,13-trans-prostadienoate                        250  900         128       methyl 9-oxo-15-triphenylmethoxy-20-methyl-8.xi                               .-5-                                                                          cis,13-trans-prostadienoate                        251  900         130       methyl 9-oxo-15-triphenylmethoxy-16-ethyl-8ξ                               -5-                                                                           cis,13-trans-prostadienoate                        252  900         132       methyl 9-oxo-15-triphenylmethoxy-16-methyl-20-                                n                                                                             nor-8ξ-cis,13-trans-prostadienoate              253  900         134       methyl 9-oxo-15-triphenylmethoxy-19-methyl-8.xi                               .-5-                                                                          cis,13-trans,18-prostatrienoate                    254  900         135       methyl 9-oxo-15-triphenylmethoxy-18,19-dimethyl                               -                                                                             8ξ-5-cis,13-trans,18-prostatrienoate            255  900         137       methyl 9-oxo-15-triphenylmethoxy-19,20-dinor-8.                               xi.-                                                                          5-cis,13-trans,17-prostatrienoate                  256  900         139       methyl 9-oxo-15-triphenylmethoxy-8ξ-5-cis,13                               -                                                                             trans,17-cis-prostatrienoate                       __________________________________________________________________________

EXAMPLE 257 Preparation of ethyl 9α/β,15-dihydroxy-13-trans-prostenoate

A soluton containing 3 g. of ethyl 9-oxo-15-hydroxy-13-trans-prostenoate(Example 121) in 120 ml. of absolute alcohol containing 115 mg. ofsodium borohydride is stirred at ambient temperature for 18 hours. Thesolution is poured into 300 ml. of saturated sodium chloride solutionand the oily precipitate is extracted with ether. The ether is washedwith saturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness to give subject product as an oil; λ max.2195, 5178, 8.45 μ; the product is a mixture of 9α- and 9β-hydroxyderivatives.

EXAMPLES 258-374

Treatment of the designated 9-oxo-15-triphenylmethoxy derivatives listedin the table below, with glacial acetic acid-tetrahydropyran-water(4:2:1) in the manner described in Example 121 is productive of thecorresponding 15-hydroxy derivatives of the table. This acid treatmentalso ensures a trans-relationship between the two side-chains attachedto C₈ and C₁₂.

                  TABLE 4                                                         ______________________________________                                                  Starting 15-tri-                                                              phenylmethoxy Product Alkyl 9-oxo-                                  Ex-       derivative of 15-hydroxy-13-trans-                                  ample     Example       prostenoates                                          ______________________________________                                        258       140           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-13-trans-                                                        prostenoate                                           259       141           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-13-                                                             trans-prostenoate                                     260       142           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-13-trans-                                                             prostenoate                                           261       143           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-13-trans-                                                        prostenote                                            262       144           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-13-trans-                                                               prostenoate                                           263       145           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-13-trans-                                                               prostenoate                                           264       146           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-13-trans-                                                            prostenoate                                           265       147           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-13-trans-                                                             prostenoate                                           266       148           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-13-trans-                                                            prostenoate                                           267       149           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-13-trans-                                                            prostenoate                                           268       150           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-15-trans-                                                            prostenoate                                           269       151           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        13-trans-prostenoate                                  270       152           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-13-                                                            trans-prostenoate                                     271       153           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-13-                                                            trans-prostenoate                                     272       154           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-13-trans-                                                              prostenoate                                           273       155           Butyl 9-oxo-15-hydroxy-                                                       13-trans-prostenoate                                  274       156           Isopropyl 9-oxo-15-                                                           hydroxy-13-trans-                                                             prostenoate                                           275       157           Methyl 9-oxo-15-hydroxy-                                                      13-trans-prostenoate                                  276       158           n-decyl 9-oxo-15-                                                             hydroxy-13-trans-                                                             prostenoate                                           277       159           Methyl 9-oxo-15-                                                              hydroxy-5-cis,-13-                                                            trans-prostadienoate                                  278       160           Ethyl 9-oxo-15-hydroxy-                                                       20-nor-13-trans-                                                              prostenoate                                           279       161           Ethyl 9-oxo-15-hydroxy-                                                       20-methyl-13-trans-                                                           prostenoate                                           280       162           Ethyl-9-oxo-15-hydroxy-                                                       16-ethyl-13-trans-                                                            prostenoate                                           281       163           Ethyl 9-oxo-15-hydroxy-                                                       16-methyl-20-nor-13-                                                          trans-prostenoate                                     282       164           Ethyl 9-oxo-15-hydroxy-                                                       19-methyl-13-trans,18-                                                        prostadienoate                                        283       165           Ethyl 9-oxo-15-hydroxy-                                                       18,19-dimethyl-13-                                                            trans,18-prostadienoate                               284       166           Ethyl 9-oxo-15-hydroxy-                                                       13-trans,17-cis-                                                              prostadienoate                                        285       167           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-13-trans,                                                        17-cis-prostadienoate                                 286       168           Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-13-trans-                                                           17-cis-prostadienoate                                 287       169           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-13-                                                             trans,17-cis-prosta-                                                          dienoate                                              288       170           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-13-trans,17-                                                          cis-prostadienoate                                    289       171           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-13-trans-                                                        17-cis-prostadienoate                                 290       172           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-13-trans,17-cis                                                         prostadienoate                                        291       173           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-13-trans,17-cis-                                                        prostadienoate                                        292       174           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-13-trans,17-                                                         cis-prostadienoate                                    293       175           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-13-trans,17-                                                          cis-prostadienoate                                    294       176           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-13-trans,17-                                                         cis-prostadienoate                                    295       177           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-13-trans-17-                                                         cis-prostadienoate                                    296       178           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-13-trans,17-                                                         cis-prostadienoate                                    297       179           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        13-trans,17-cis-prosta-                                                       dienoate                                              298       180           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-13-                                                            trans,17-cis-prosta-                                                          dienoate                                              299       181           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-13-                                                            trans,17-cis-prosta-                                                          dienoate                                              300       182           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-13-trans,17-                                                           cis,prostadienoate                                    301       183           Butyl 9-oxo-15-hydroxy-                                                       13-trans,17-cis-                                                              prostadienoate                                        302       184           Isopropyl 9-oxo-15-                                                           hydroxy-13-trans,17-                                                          cis-prostadienoate                                    303       185           Methyl 9-oxo-15-hydroxy-                                                      13-trans,17-cis-                                                              prostadienoate                                        304       186           n-decyl 9-oxo-15-                                                             hydroxy-13-trans,17-                                                          cis-prostadienoate                                    305       187           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-19-iso-                                                          butyl-13-trans,18-                                                            prostadienoate                                        306       188           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7,19,20-pentanor-                                                         13-trans-17-prosta-                                                           dienoate                                              307       189           Ethyl 9-oxo-15-hydroxy-                                                       19,20-dinor-13-trans,                                                         18-prostadienoate                                     308       190           Ethyl 9-oxo-15-hydroxy-                                                       17-methyl-20-isopro-                                                          penyl-13-trans-prosta-                                                        dienoate                                              309       191           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-6,7,19,20-                                                           tetranor-13-trans-                                                            prostenoate                                           310       192           Ethyl 9-oxo-15-hydroxy-                                                       18,19-dimethyl-6,7-                                                           dinor-13-trans,18-                                                            prostadienoate                                        311       193           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-7a,7b-bishomo-                                                       13-trans-prostenoate                                  312       194           Ethyl 9-oxo-15-hydroxy-                                                       19-methyl-7a,7b-bis-                                                          homo-13-trans,18-                                                             prostadienoate                                        313       195           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-19,20-dinor-                                                          13-trans-prostenoate                                  314       196           Ethyl 9-oxo-15-hydroxy-                                                       2,20-diethyl-13-trans-                                                        prostenoate                                           315       197           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-methyl-20-                                                         nor-trans-prostenoate                                 316       198           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-18,19-dimethyl-                                                       13-trans,18-prosta-                                                           dienoate                                              317       199           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-18,19,20-                                                        trinor-13-trans-                                                              prostenoate                                           318       200           Ethyl 9-oxo-15-hydroxy-                                                       3,3,20-trimethyl-13-                                                          trans-prostenoate                                     319       201           Ethyl 9-oxo-15-hydroxy-                                                       3,3,16-trimethyl-20-                                                          nor-13-trans-prosta-                                                          noate                                                 320       202           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19-iso-                                                          butyl-13-trans,18-                                                            prostadienoate                                        321       203           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19,20-                                                           dinor-13-trans,17-                                                            prostadienoate                                        322       204           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-20-nor-13-trans-                                                        prostenoate                                           323       205           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-20-methyl-13-                                                           trans-prostenoate                                     324       206           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-ethyl-13-                                                            trans-prostenoate                                     325       207           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-methyl-20-                                                           nor-13-trans-                                                                 prostenoate                                           326       208           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-19,20-dinor-13-                                                         trans,17-prostadienoate                               327       209           Ethyl 9-oxo-15-hydroxy-                                                       7,19,20-trinor-13-                                                            trans,17-prosadienoate                                328       210           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-18,19-dimethyl-                                                         13-trans,18-prosta-                                                           dienoate                                              329       211           Ethyl 9-oxo-15-hydroxy-                                                       7,18,19,20-tetranor-                                                          16-methyl-13-trans-                                                           prostenoate                                           330       212           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-20-nor-13-                                                           trans-prostenoate                                     331       213           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-20-ethyl-13-                                                         trans-prostenoate                                     332       214           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-ethyl-19,                                                         20-dinor-13-trans-                                                            prostenoate                                           333       215           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-methyl-20-                                                        nor-13-trans-prostenoate                                                      prostenoate                                           334       216           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-19-methyl-13-                                                        trans,18-prostadienote                                335       217           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-18,19-dimethyl-                                                       13-trans,18-prosta-                                                           dienoate                                              336       218           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-19,20-dinor-                                                          13-trans,17-prosta-                                                           dienoate                                              337       219           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-20-nor-13-                                                           trans-prostenoate                                     338       220           Ethyl 9-oxo-15-hydroxy                                                        2-phenyl-20-ethyl-13-                                                         trans-prostenoate                                     339       221           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-ethyl-13-                                                         trans-prostenoate                                     340       222           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-methyl-18,                                                        19,20-trinor-13-trans-                                                        prostenoate                                           341       223           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-18,19-di                                                             methyl-13-trans,18-pro-                                                       stadienoate                                           342       224           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-20-nor-13-                                                           trans-prostenoate                                     343       225           Ethyl 9-oxo-15-hydroxy-                                                       2,20-dimethyl-13-trans-                                                       prostenoate                                           344       226           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-ethyl-19,                                                         20-dinor-13-trans-                                                            prostenoate                                           345       227           Ethyl 9-oxo-15-hydroxy-                                                       2,19-dimethyl-13-trans-                                                       18-prostadienoate                                     346       228           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoate                                              347       229           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-nor-13-                                                           trans-prostenoate                                     348       230           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-methyl-13-                                                        trans-prostenoate                                     349       231           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-ethyl-13-                                                         trans-prostenoate                                     350       232           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-18,19-dimethyl-                                                      13-trans,18-prosta-                                                           dienoate                                              351       233           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoate                                              352       234           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        20-ethyl-13-trans-                                                            prostenoate                                           353       235           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7,20-                                                            tetranor-16-methyl-13-                                                        trans-prostenoate                                     354       236           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        19-isobutyl-13-trans,                                                         18-prostadienoate                                     355       237           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-methyl-13-                                                        trans-prostenoate                                     356       238           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-19-methyl-13-                                                        trans,18-prostadienoate                               357       239           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-20-nor-                                                        13-trans-prostenoate                                  358       240           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-20-                                                            ethyl-13-trans-pro-                                                           stenoate                                              359       241           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-                                                            methyl-20-nor-13-trans-                                                       prostenoate                                           360       242           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-19-                                                            methyl-13-trans,18-                                                           prostadienoate                                        361       243           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-20-nor-13-trans-                                                       prostenoate                                           362       244           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-20-methyl-13-                                                          trans-prostenoate                                     363       245           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-ethyl-13-                                                           trans-prostenoate                                     364       246           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-methyl-18,19,                                                       20-trinor-13-trans-                                                           prostenoate                                           365       247           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19-methyl-13-                                                          trans,18-prostadienoate                               366       248           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19,20-dinor-13-                                                        trans,17-prostadienoate                               367       249           Methyl 9-oxo-15-hydroxy-                                                      20-nor-5-cis,13-trans-                                                        prostadienoate                                        368       250           Methyl 9-oxo-15-hydroxy-                                                      20-methyl-5-cis,13-                                                           trans-prostadienoate                                  369       251           Methyl 9-oxo-15-hydroxy-                                                      16-ethyl-5-cis-13-                                                            trans-prostadienoate                                  370       252           Methyl 9-oxo-15-hydroxy-                                                      16-methyl-20-nor-5-cis                                                        13-trans-prostadienoate                               371       253           Methyl 9-oxo-15-hydroxy-                                                      19-methyl-5-cis,13-                                                           trans,18-prosta-                                                              trienoate                                             372       254           Methyl 9-oxo-15-hydroxy-                                                      18,19-dimethyl-5-cis,                                                         13-trans,18-prosta-                                                           trienoate                                             373       255           Methyl 9-oxo-15-hydroxy-                                                      19,20-dinor-5-cis,13-                                                         trans,17-prosta-                                                              trienoate                                             374       256           Methyl 9-oxo-15-hydroxy-                                                      5-cis,13-trans,17-cis-                                                        prostatrienoate                                       ______________________________________                                    

EXAMPLES 375-491

Saponification of the alkyl esters designated in the following table bythe method described in Example 122 is productive of the prostnoic acidsof the table.

                  Table 5                                                         ______________________________________                                                  Starting alkyl 9-                                                                           Product                                               Ex-       oxo-prostenoate                                                                             9-oxo-15-hydroxy-13-                                  ample     of example    trans-prostenoic acid                                 ______________________________________                                        375       258           9-oxo-15-hydroxy-5,6,7-                                                       trinor-13-trans-pros-                                                         tenoic acid                                           376       259           9-oxo-15-hydroxy-7a,7b-                                                       bishomo-13-trans-pros-                                                        tenoic acid                                           377       260           9-oxo-15-hydroxy-2-                                                           ethyl-13-trans-pros-                                                          tenoic acid                                           378       261           9-oxo-15-hydroxy-3,3-                                                         dimethyl-13-trans-                                                            prostenoic acid                                       379       262           9-oxo-15-hydroxy-3-oxa-                                                       13-trans-prostenoic                                                           acid                                                  380       263           9-oxo-15-hydroxy-7-nor-                                                       13-trans-prostenoic                                                           acid                                                  381       264           9-oxo-15-hydroxy-2-                                                           fluoro-13-trans-pros-                                                         tenoic acid                                           382       265           9-oxo-15-hydroxy-7a-                                                          homo-13-trans-pros-                                                           tenoic acid                                           383       266           9-oxo-15-hydroxy-2-                                                           phenyl-13-trans-pros-                                                         tenoic acid                                           384       267           9-oxo-15-hydroxy-2-                                                           methyl-13-trans-pros-                                                         tenoic acid                                           385       268           9-oxo-15-hydroxy-10a-                                                         homo-13-trans-pros-                                                           tenoic acid                                           386       269           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-13-                                                         trans-prostenoic acid                                 387       270           9-oxo-hydroxy-10a-                                                            homo-7-nor-13-trans-                                                          prostenoic acid                                       388       271           9-oxo-15-hydroxy-7a,-                                                         10a-bishomo-13-trans-                                                         prostenoic acid                                       389       272           9-oxo-15-hydroxy-3-                                                           thia-13-trans-pros-                                                           tenoic acid                                           390       273           9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                 391       274           9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                 392       275           9-oxo-15-hdyroxy-13-                                                          trans-prostenoic acid                                 393       276           9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                 394       277           9-oxo-15-hydroxy-5-cis,                                                       13-trans-prostadienoic                                                        acid                                                  395       278           9-oxo-15-hydroxy-20-nor-                                                      13-trans-prostenoic                                                           acid                                                  396       279           9-oxo-15-hydroxy-20-                                                          methyl-13-trans-pros-                                                         tenoic acid                                           397       280           9-oxo-15-hydroxy-16-                                                          ethyl-13-trans-pros-                                                          tenoic acid                                           398       281           9-oxo-15-hydroxy-16-                                                          methyl-20-nor-13-trans-                                                       prostenoic acid                                       399       282           9-oxo-15-hydroxy-19-                                                          methy-13-trans,18- -  prostadienoic acid              400       283           9-oxo-15-hydroxy-18,19-                                                       dimethyl-13-trans,18-                                                         prostadienoic acid                                    401       284           9-oxo-hydroxy-13-                                                             trans,17-cis-prosta-                                                          dienoic acid                                          402       285           9-oxo-15-hydroxy-5,6,7-                                                       trinor-13-trans,17-cis-                                                       prostadienoic acid                                    403       286           9-oxo-15-hydroxy-6,7-di-                                                      nor-13-trans,17-cis-                                                          prostadienoic acid                                    404       287           9-oxo-15-hydroxy-7a,7b-                                                       bishomo-13-trans,17-                                                          cis-prostadienoic acid                                405       288           9-oxo-15-hydroxy-2-                                                           ethyl-13-trans,17-cis-                                                        prostadienoic acid                                    406       289           9-oxo-15-hydroxy-3,3-                                                         dimethyl-13-trans,17-                                                         cis-prostadienoic acid                                407       290           9-oxo-15-hydroxy-3-oxa-                                                       13-trans,17-cis-pros-                                                         tadienoic acid                                        408       291           9-oxo-15-hydroxy-7-nor-                                                       13-trans,17-cis-pros-                                                         tadienoic acid                                        409       292           9-oxo-15-hydroxy-2-                                                           fluoro-13-trans,17-cis-                                                       prostadienoic acid                                    410       293           9-oxo-15-hydroxy-7a-                                                          homo-13-trans,17-cis-                                                         prostadienoic acid                                    411       294           9-oxo-15-hydroxy-2-                                                           phenyl-13-trans,17-cis-                                                       prostadienoic acid                                    412       295           9-oxo-15-hydroxy-2-                                                           methyl-13-trans,17-                                                           cis-prostadienoic acid                                413       296           9-oxo-15-hydroxy-10a-                                                         homo-13-trans,17-cis-                                                         prostadienoic acid                                    414       297           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-13-                                                         trans,17-cis-prosta-                                                          dienoic acid                                          415       298           9-oxo-15-hydroxy-10a-                                                         homo-7-nor-13-trans,-                                                         17-cis-prostadienoic                                                          acid                                                  416       299           9-oxo-15-hydroxy-7a,-                                                         10a-bishomo-13-trans,-                                                        17-cis-prostadienoic                                                          acid                                                  417       300           9-oxo-15-hydroxy-3-thia-                                                      13-trans,17-cis-prosta-                                                       dienoic acid                                          418       301           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                          419       302           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                          420       303           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                          421       304           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                          422       305           9-oxo-15-hydroxy-5,6,7-                                                       trinor-19-isobutyl-13-                                                        trans,18-prostadienoic                                                        acid                                                  423       306           9-oxo-15-hydroxy-5,6,7,-                                                      19,20-pentanor-13-trans,                                                      17-prostadienoic acid                                 424       307           9-oxo-15-hydroxy-19,20-                                                       dinor-13-trans,18-                                                            prostadienoic acid                                    425       308           9-oxo-15-hydroxy-17,-                                                         methyl-20-isopropenyl-                                                        13-trans-prostenoic                                                           acid                                                  426       309           9-oxo-15-hydroxy-16-                                                          ethyl-6,7,19,20-tetra-                                                        nor-13-trans-prostenoic                                                       acid                                                  427       310           9-oxo-15-hydroxy-18,19-                                                       dimethyl-6,7-dinor-13-                                                        trans,18-prostadienoic                                                        acid                                                  428       311           9-oxo-15-hydroxy-16-                                                          ethyl-7a,7b-bishomo-                                                          13-trans-prostenoic                                                           acid                                                  429       312           9-oxo-15-hydroxy-19-                                                          methyl-7a,7b-bishomo-                                                         13-trans,18-prosta-                                                           dienoic acid                                          430       313           9-oxo-15-hydroxy-2-                                                           ethyl-19,20-dinor-13-                                                         trans-prostenoic acid                                 431       314           9-oxo-15-hydroxy-2,20-                                                        diethyl-13-trans-pros-                                                        enoic acid                                            432       315           9-oxo-15-hydroxy-2-                                                           ethyl-16-methyl-20-nor-                                                       13-trans-prostenoic                                                           acid                                                  433       316           9-oxo-15-hydroxy-2-                                                           ethyl-18,19-dimethyl-                                                         13-trans,18-prosta-                                                           dienoic acid                                          434       317           9-oxo-15-hydroxy-3,3-                                                         dimethyl-18,19,20-tri-                                                        nor-13-trans-prostenoic                                                       acid                                                  435       318           9-oxo-15-hydroxy-3,3,-                                                        20-trimethyl-13-trans-                                                        prostenoic acid                                       436       319           9-oxo-15-hydroxy-3,3,-                                                        16-trimethyl-20-nor-13-                                                       trans-prostenoic acid                                 437       320           9-oxo-15-hydroxy,3,3-                                                         dimethyl-19-isobutyl-                                                         13-trans,18-prosta-                                                           dienoic acid                                          438       321           9-oxo-15-hydroxy-3,3-                                                         dimethyl-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoic acid                                          439       322           9-oxo-15-hydroxy-3-oxa-                                                       20-nor-13-trans-prost-                                                        enoic acid                                            440       323           9-oxo-15-hydroxy-3-oxa-                                                       20-methyl-13-trans-                                                           prostenoic acid                                       441       324           9-oxo-15-hydroxy-3-oxa-                                                       16-ethyl-13-trans-                                                            prostenoic acid                                       442       325           9-oxo-15-hydroxy-3-oxa-                                                       16-methyl-20-nor-13-                                                          trans-prostenoic acid                                 443       326           9-oxo-15-hydroxy-3-oxa-                                                       19,20-dinor-13-trans,-                                                        17-prostadienoic acid                                 444       327           9-oxo-15-hydroxy-7,19,-                                                       20-trinor-13-trans,17-                                                        prostadienoic acid                                    445       328           9-oxo-15-hydroxy-7-nor- -  18,19-dimethyl-13-                                 trans,18-prostadienoic                                                        acid                                                  446       329           9-oxo-15-hydroxy-7,18,-                                                       19,20-tetranor-16-meth-                                                       yl-13-trans-prostanoic                                                        acid                                                  447       330           9-oxo-15-hydroxy-2-                                                           fluoro-20-nor-13-trans-                                                       prostenoic acid                                       448       331           9-oxo-15-hydroxy-2-                                                           fluoro-20-ethyl-13-                                                           trans-prostenoic acid                                 449       332           9-oxo-15-hydroxy-2-                                                           fluoro-16-ethyl-19,20-                                                        dinor-13-trans-pros-                                                          tenoic acid                                           450       333           9-oxo-15-hydroxy-2-                                                           fluoro-16-methyl-20-                                                          nor-13-trans-pros-                                                            tenoic acid                                           451       334           9-oxo-15-hydroxy-2-                                                           fluoro-19-methyl-13-                                                          trans,18-prostadienoic                                                        acid                                                  452       335           9-oxo-15-hydroxy-7a-                                                          homo-18,19-dimethyl-                                                          13-trans,18-prosta-                                                           dienoic acid                                          453       336           9-oxo-15-hydroxy-7a-                                                          homo-19,20-dinor-13-                                                          trans,17-prostadienoic                                                        acid                                                  454       337           9-oxo-15-hydroxy-2-                                                           phenyl-20-nor-13-trans-                                                       prostenoic acid                                       455       338           9-oxo-15-hydroxy-2-                                                           phenyl-20-ethyl-13-                                                           trans-prostenoic acid                                 456       339           9-oxo-15-hydroxy-2-                                                           phenyl-16-ethyl-13-                                                           trans-prostenoic acid                                 457       340           9-oxo-15-hydroxy-2-phen-                                                      yl-16-methyl-18,19,20-                                                        trinor-13-trans-pros-                                                         tenoic acid                                           458       341           9-oxo-15-hydroxy-2-                                                           phenyl-18,19-dimethyl-                                                        13-trans,18-prosta-                                                           dienoic acid                                          459       342           9-oxo-15-hydroxy-2-                                                           methyl-20-nor-13-trans-                                                       prostenoic acid                                       460       343           9-oxo-15-hydroxy-2,20-                                                        dimethyl-13-trans-                                                            prostenoic acid                                       461       344           9-oxo-15-hydroxy-2-                                                           methyl-16-ethyl-19,20-                                                        dinor-13-trans-pros-                                                          tenoic acid                                           462       345           9-oxo-15-hydroxy-2,19-                                                        dimethyl-13-trans,18-                                                         prostadienoic acid                                    463       346           9-oxo-15-hydroxy-2-                                                           methyl-19,20-dinor-                                                           13-trans,17-prosta-                                                           dienoic acid                                          464       347           9-oxo-15-hydroxy-10a-                                                         homo-20-nor-13-trans-                                                         prostenoic acid                                       465       348           9-oxo-15-hydroxy-10a-                                                         homo-20-methyl-13-                                                            trans-prostenoic acid                                 466       349           9-oxo-15-hydroxy-10a-                                                         homo-16-ethyl-13-trans-                                                       prostenoic acid                                       467       350           9-oxo-15-hydroxy-10a-                                                         homo-18,19-dimethyl-                                                          13-trans,18-prosta-                                                           dienoic acid                                          468       351           9-oxo-15-hydroxy-10a-                                                         homo-19,20-dinor-13-                                                          trans,17-prostadienoic                                                        acid                                                  469       352           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-20-                                                         ethyl-13-trans-pros-                                                          tenoic acid                                           470       353           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7,20-tetra-                                                          nor-16-methyl-13-trans-                                                       prostenoic acid                                       471       354           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-19-                                                         isobutyl-13-trans,18-                                                         prostadienoic acid                                    472       355           9-oxo-15-hydroxy-10a-                                                         homo-20-methyl-13-                                                            trans-prostenoic acid                                 473       356           9-oxo-15-hydroxy-10a-                                                         homo-19-methyl-13-                                                            trans,18-prostadienoic                                                        acid                                                  474       357           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-20-nor-13-                                                            trans-prostenoic acid                                 473       358           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-20-ethyl-13-                                                          trans-prostenoic acid                                 476       359           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-methyl-20-                                                         nor-13-trans-prostenoic                                                       acid                                                  477       360           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-19-methyl-13-                                                         trans,18-prostadienoic                                                        acid                                                  478       361           9-oxo-15-hydroxy-3-thia-                                                      20-nor-13-trans-pros-                                                         tenoic acid                                           479       362           9-oxo-15-hydroxy-3-thia-                                                      20-methyl-13-trans-                                                           prostenoic acid                                       480       363           9-oxo-15-hydroxy-3-thia-                                                      16-ethyl-13-trans-                                                            prostenoic acid                                       481       364           9-oxo-15-hydroxy-3-thia-                                                      16-methyl-18,19,20-                                                           trinor-13-trans-pros-                                                         tenoic acid                                           482       365           9-oxo-hydroxy-3-thia-                                                         19-methyl-13-trans,18-                                                        prostadienoic acid                                    483       366           9-oxo-15-hydroxy-3-thia-                                                      19,20-dinor-13-trans,-                                                        17-prostadienoic acid                                 484       367           9-oxo-15-hydroxy-20-nor-                                                      5-cis,13-trans-prosta-                                                        dienoic acid                                          485       368           9-oxo-15-hydroxy-20-                                                          methyl-5-cis,13-trans-                                                        prostadienoic acid                                    486       369           9-oxo-15-hydroxy-16-                                                          ethyl-5-cis,13-trans-                                                         prostadienoic acid                                    487       370           9-oxo-15-hydroxy-16-                                                          methyl-20-nor-5-cis,13-                                                       trans-prostadienoic                                                           acid                                                  488       371           9-oxo-15-hydroxy-19-                                                          methyl-5-cis,13-trans,-                                                       18-prostatrienoic acid                                489       372           9-oxo-15-hydroxy-18,19-                                                       dimethyl-5-cis,13-                                                            trans-18-prostatrienoic                                                       acid                                                  490       373           9-oxo-15-hydroxy-19,20-                                                       dinor-5-cis,13-trans,-                                                        17-prostatrienoic acid                                491       374           9-oxo-15-hydroxy-5-cis,-                                                      13-trans,17-cis-prosta-                                                       trienoic acid                                         ______________________________________                                    

EXAMPLE 492 Preparation of 3-(tert-butoxy)-1-iodooctane

Into a solution of 16.7 g. of 1-iodo-3-octanol [Shriner et al., J. Org.Chem. 4, 103 (1939)] in 250 ml. of methylene chloride is bubbledisobutylene at a fast rate until the solution is saturated. The solutionis cooled and 2 ml. of concentrated sulfuric acid is added. The solutionis stoppered and allowed to stand at room temperature for 3 days. Afterthe solution is poured into 300 ml. of 5% sodium carbonate, the organicphase is separated, washed with brine, dried with anhydrous magnesiumsulfate and evaporated to dryness. Distillation gave 13.9 g. (68%) ofproduct, b.p. 59° C. (0.008 mm).

EXAMPLE 493 Preparation of 15-(tert-butoxy)-9-oxoprostanoic acid, ethylester

To a Grignard solution, prepared from 5.05 g. of magnesium and 65.8 g.of 3-(tert-butoxy)-1-iodooctane in 150 ml. of diethyl ether undernitrogen atmosphere, is added 4.0 g. of copperiodide-tri-n-butylphosphine complex followed by dropwise addition of 49g. of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one [Hardegger et al., Helv.Chim. Acta 50, 2501 (1967)] and the resulting mixture is stirred for 18hours. Saturated ammonium chloride (110 ml.) is added followed by 100ml. of water and 100 ml. of diethyl ether. Unreacted magnesium isremoved by filtration. The ethereal layer is washed successively withaqueous sodium thiosulfate solution, ammonium chloride solution, andwater, dried over magnesium sulfate and taken to dryness to give an oil.Distillation at 0.05 mm. (bath 100°-185° C.) gives 45.4 g. of materialcontaining unreacted starting material and 30 g. (85% yield based onnon-recovered starting material; see below) of residue which containsthe desired product. This material is chromatographed on silica gel. Theproduct is eluted with diethyl ether to give 25.2 g. (71% based onrecovered starting material) of a syrup; this material has nosignificant ultraviolet absorption; λ_(max) ^(KBr) 5.74, 7.20, 7.35,8.35 μ; nmr 2H quartet δ4.09 (OCH₂ of ester), 1H broad singlet 3.57(carbinolic proton), 5H overlapping multiplets 2.0-2.4 (protons next toC-O), 3H triplet 1.22 (CH₃ of ethyl), OH singlet 1.17 (CH₃ 's tot-butyl) and 3H triplet 0.9 (terminal methyl); mass spectrum: m/e 424.

EXAMPLE 494 Preparation of 15-hydroxy-9-oxoprostanoic acid, ethyl ester

A solution of 25 g. of 15-(tert-butoxy)-9-oxoprostanoic acid, ethylester in 100 ml. of trifluoroacetic acid is stirred in an ice bath for 1hour and is then poured into 500 ml. of ice water and extracted severaltimes with chloroform. The combined chloroform extracts are washed withsaturated sodium bicarbonate solution, saturated sodium chloridesolution, dried with anhydrous magnesium sulfate, and taken to dryness.The resulting oil is dissolved in 200 ml. of 1N ammonium hydroxide inethanol, kept at ambient temperature for 15 minutes, then taken todryness. The residual oil is dissolved in chloroform and washed with 1Nhydrochloric acid, saturated sodium chloride solution, dried and takento dryness to give 21.7 g. (100%) of product as a yellow syrup. There isessentially no uv absorption; λ_(max) ^(KBr) 2.90, 5.75, 8.45 μ; nmr 2Hquartet δ4.13 (OCH₂ of ester), 1H broad singlet 3.63 (carbinolicproton), 3H triplet (CH₃ of ester), and 3H distorted triplet 0.92(terminal methyl); mass spectrum: m/e 368.

EXAMPLE 495 Preparation of 15-hydroxy-9-oxoprostanoic acid

A suspension of 15 g. of 15-hydroxy-9-oxoprostanoic acid, ethyl ester in230 ml. of aqueous methanol (1:1) containing 6.45 g. of potassiumhydroxide is stirred at 50° C. for 1 hour and then at room temperaturefor 18 hours. The resulting solution is acidified with 1N hydrochloricacid, saturated with sodium chloride, and extracted several times withdiethyl ether. The combined ether extracts are washed twice withsaturated sodium chloride solution, dried with anhydrous magnesiumsulfate, and taken to dryness to give 13.1 g. (94%) of product as anoil. There is essentially no uv absorption; [a]_(D) ²⁵ 0° (1.0% inCHCl₃); λ_(max) ^(KBr) 2.80-3.70 (broad), 5.75, 5.87 μ; nmr 2H singletδ6.65 (hydroxyl and carboxyl protons), 1H broad singlet 3.63 (carbinolicproton), and 3H distorted triplet 0.93 (terminal methyl); mass spectrum;m/e 340.

EXAMPLE 496 Preparation of 1chloro-3-hydroxy-4-octyne

To 68 ml. of 1.6M butyllithium in hexane at -50° C. is added dropwise,with stirring, 7.4 g. of 1-pentyne. The resulting white sludge isdiluted with 20 ml. of hexane, brought to 10° C. and treated with 11 g.of freshly prepared β-chloropropionaldehyde (Org. Syn., Coll. Vol. I, p.166) at such a rate that the temperature is maintained at 10°-15° C. Thesolution is allowed to stir at ambient temperature for 18 hours thentreated with saturated ammonium chloride solution. The organic phase isseparated, washed with dilute hydrochloric solution, dried withanhydrous magnesium sulfate and taken to dryness. Distillation gives 5.1g of product b.p. 65°-68° C. at 0.3 nm.; λmax. 2.95 (--OH) and 4.55 μ(--C.tbd.C--); vapor phase chromatography shows one peak.

EXAMPLE 497 Preparation of 1-chloro-3-hydroxy-4-cis-octene

A solution of 2 g. of 1-chloro-3-hydroxy-4-octyne (Example 496) ishydrogenated in 50 ml. absolute alcohol using 200 mg. of Lindlarcatalyst (5% Pd on CaCO₃). The catalyst is removed by filtration and themother liquor is taken to dryness to give 2 g. of an oil; λmax. 2.95(--OH) and 7.25 μ ##STR34##

EXAMPLE 498 Preparation of 3-hydroxy-1-iodo-4-octyne

A mixture of 15 g. of sodium iodide in 100 ml. of 2-butanone is stirredat the reflux temperature for 30 minutes. To the cooled mixture is added12 g. of 1-chloro-3-hydroxy-4-octyne in 150 ml. of 2-butanone. Theresulting mixture is stirred at the reflux temperature for 18 hours thencooled and filtered. The mother liquor is taken to dryness and theresidue is triturated with benzene and filtered. The benzene is taken todryness to give the subject product as an oil. The material is shown tobe homogeneous by vapor phase chromatography and thin layerchromatography.

EXAMPLE 499 Preparation of 3-hydroxy-1-iodo-4-cis-octen

The subject compound is prepared from 3-hydroxy-1-chloro-4-cis-octeneand sodium iodide by the method of Example 498.

EXAMPLE 500 Preparation of 3-t-butoxy-1-iodo-4-octyne

The subject compound is prepared from 3-hydroxy-1-iodo-4-octyne (Example498) and isobutylene by the method of Example 492.

EXAMPLE 501 Preparation of 3-t-butoxy-1-iodo-4-cis-octene

The subject compound is prepared from 3-hydroxy-1-iodo-4-cis-octene(Example 499) and isobutylene by the method of Example 492.

EXAMPLE 502 Preparation of 3-(tert-butoxy)-1-iodohexane

A mixture of 23.4 g. of 1-chloro-3-hexanol [Fourneau, et. al., Bull.Soc. Chem. France, 25, 367 (1919)] in 300 ml. of 2-butanone containing30 g. of sodium iodide is stirred at the reflux temperature for 18hours. The cooled solution is filtered and the mother liquor is taken todryness. Distillation of the residue affords 32.9 g. (84%) of1-iodo-3-hexanol, b.p. 105° C. (10 mm). Treatment of this material in500 ml. of methylene chloride, containing 4 ml. of concentrated sulfuricacid, with isobutylene according to the procedure described in Example492 gives 27 g. of crude material. Chromatography on florisil affords 16g. of product; λmax. 7.22 and 7.37 μ (tert-butyl group).

EXAMPLES 503-558

Treatment of the cyclopentenones designated in the table below with thedesignated Grignard reagents by the procedure of Example 493 isproductive of the alkyl 9-oxo-15-t-butoxy-8ξ-prostanoates andprostanoates of the table. 3-t-Butoxyoctylmagnesium iodide was preparedfrom 3-t-butoxy-1-iodooctane (Example 492); 3-t-butoxyhexyl magnesiumiodide was prepared from 3-t-butoxy-1-iodohexane (Example 502),3-t-butoxy-4-octynyl magnesium iodide was prepared from3-t-butoxy-1-iodo-4-octyne (Example 500); and 3-t-butoxy-4-cis-octenylmagnesium iodide was prepared from 3-t-butoxy-1-iodo-4-cis-octene(Example 501).

                                      Table 6                                     __________________________________________________________________________         Starting cyclopentenone                                                                              Product Alkyl 9-Oxo-15-t-butoxy-8ξ-prostano                                ates,                                             Example                                                                            of Example   Orignard Reagent                                                                        prostynoates end prostenoates                     __________________________________________________________________________    503  31           3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-prostano                                ate                                                                 magnesium iodide                                            504  41           3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-                         magnesium iodide                                                                        prostanoate                                       505  46           3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-prostanoat                                e                                                                   magnesium iodide                                            506  70           3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-prostan                                oate                                                                magnesium iodide                                            507  79           3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-prostan                                oate                                                                magnesium iodide                                            508  99           3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-prostan                                oate                                                                magnesium iodide                                            509  118          3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-prostanoa                                te                                                                  magnesium iodide                                            510  900          3-t-butoxyoctyl                                                                         methyl 9-oxo-15-t-butoxy-8ξ-5-cis-prostenoa                                te                                                                  magnesium iodide                                            511  31           3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-ethyl-19,20-dinor-8.                                xi.-                                                                magnesium iodide                                                                        prostanoate                                       512  41           3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-19,20-                         magnesium iodide                                                                        dinor-8ξ-prostanoate                           513  46           3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-3,oxa-19,20-dinor-8.xi                                .-                                                                  magnesium iodide                                                                        prostanoate                                       514  70           3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-fluoro-19,20-dinor-8                                ξ-                                                               magnesium iodide                                                                        prostanoate                                       515  79           3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-phenyl-19,20-dinor-8                                -86 -                                                               magnesium iodide                                                                        prostanoate                                       516  99           3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-methyl-19,20-dinor-8                                ξ-                                                               magnesium iodide                                                                        prostanoate                                       517  118          3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-3-thia-19,20-dinor-8.x                                i.-                                                                 magnesium iodide                                                                        prostanoate                                       518  900          3-t-butoxyhexyl                                                                         methyl 9-oxo-15-t-butoxy-19,20-dinor-8ξ-5-c                                is-                                                                 magnesium iodide                                                                        prostenoate                                       519  13           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                        ynyl magnesium                                                                iodide                                                      520  15           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-                         ynyl magnesium                                                                          prostynoate                                                         iodide                                                      521  23           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-16                                -                                                                   ynyl magnesium                                                                          prostynaote                                                         iodide                                                      522  31           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-prost                                ynoate                                                              ynyl magnesium                                                                iodide                                                      523  41           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16-                                y                                                                   ynyl magnesium                                                                          prostynoate                                                         iodide                                                      524  46           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-prostyn                                oate                                                                ynyl magnesium                                                                iodide                                                      525  53           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-prostyn                                oate                                                                ynyl magnesium                                                                iodide                                                      526  70           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-pros                                tynoate                                                             ynyl magnesium                                                                iodide                                                      527  74           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-prost                                ynoate                                                              ynyl magnesium                                                                iodide                                                      528  79           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-pros                                tynoate                                                             ynyl magnesium                                                                iodide                                                      529  81           3-t-butoxy-4-oct-                                                                       butyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                        ynyl magnesium                                                                iodide                                                      530  82           3-t-butoxy-4-oct-                                                                       isopropyl 9-oxo-15-t-butoxy-8ξ-16-prostynoa                                te                                                                  ynyl magnesium                                                                iodide                                                      531  83           3-t-butoxy-4-oct-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                                 n                                                                   ynyl magnesium                                                                iodide                                                      532  84           3-t-butoxy-4-oct-                                                                       decyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                        ynyl magnesium                                                                iodide                                                      533  99           3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-pros                                tynoate                                                             ynyl magnesium                                                                iodide                                                      534  118          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-3-thia-8ξ                                          -16-prostynoate                                                     ynyl magnesium                                                                iodide                                                      535  111          3-t-butoxy-4-oct-                                                                       ethyl 9 oxo-15-t-butoxy-10a-homo-8ξ-16-pros                                tynoate                                                             ynyl magnesium                                                                iodide                                                      536  113          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8ξ-1                                6-                                                                  ynyl magnesium                                                                          prostynoate                                                         iodide                                                      537  114          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ-1                                6-                                                                  ynyl magnesium                                                                          prostynoate                                                         iodide                                                      538  900          3-t-butoxy-4-oct-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-16-yne-5-cis-                        ynyl magnesium                                                                          prostenoate                                                         iodide                                                      539  13           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-8ξ-16-cis-prostenoa                                te                                                                  octenyl magnesium                                                             iodide                                                      540  15           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-cis                                -                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                      541  23           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-16                                -                                                                   octenyl magnesium                                                                       cis-prostenoate                                                     iodide                                                      542  31           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-cis-                                 A                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                      543  41           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16-                                cis-                                                                octenyl magnesium                                                                       prostenoate                                                         iodide                                                      544  46           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-cis-                         octenyl magnesium                                                                       prostenoate                                                         iodide                                                      545  53           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-cis-                         octenyl magnesium                                                                       prostenoate                                                         iodide                                                      546  70           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-cis-                                g                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                      547  74           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-cis-                                 0                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                      548  79           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-cis-                                8                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                      549  81           3-t-butoxy-4-cis-                                                                       butyl 9-oxo-15-t-butoxy-8ξ-16-cis-prostenoa                                te                                                                  octenyl magnesium                                                             iodide                                                      550  82           3-t-butoxy-4-cis-                                                                       isopropyl 9-oxo-15-t-butoxy-8ξ-16-cis-                           octenyl magnesium                                                                       prostenoate                                                         iodide                                                      551  83           3-t-butoxy-4-cis-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-16-cis-                              octenyl magnesium                                                                       prostenoate                                                         iodide                                                      552  84           3-t-butoxy-4-cis-                                                                       decyl 9-oxo-15-t-butoxy-8ξ-16-cis-prostenoa                                te                                                                  octenyl magnesium                                                             iodide                                                      553  99           3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-cis-                                p                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                      554  118          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-16-cis                         octenyl magnesium                                                                       prostenoate                                                         iodide                                                      555  111          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-10a-homo-8ξ-16-cis-                                0                                                                   octenyl mgnesium                                                                        prostenoate                                                         iodide                                                      556  113          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8ξ-1                                6-                                                                  octenyl magnesium                                                                       cis-prostenoate                                                     iodide                                                      557  114          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ-1                                6-                                                                  octenyl magnesium                                                                       cis-prostenoate                                                     iodide                                                      558  900          3-t-butoxy-4-cis-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-5-cis-16-cis-                        octenyl magnesium                                                                       prostadienoate                                                      iodide                                                      __________________________________________________________________________

EXAMPLES 559-614

Treatment of the 9-oxo-15-t-butoxy derivatives designated in the tablebelow with trifluoroacetic acid and then with aqueous ammonia by themethod described in Example 494 is productive of the 9-oxo-15-hydroxyesters of the table.

                  TABLE 7                                                         ______________________________________                                                  Starting 15-t-                                                      Ex-       butoxy derivative                                                                           Product Alkyl 9-oxo-15-                               ample     of Example    hydroxy derivative                                    ______________________________________                                        559       503           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-prostanoate                                   560       504           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-prostano-                                                        ate                                                   561       505           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-prostanoate                                     562       506           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-prostanoate                                  563       507           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-prostanoate                                  564       508           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-prostanoate                                  565       509           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-prostanoate                                    566       510           Methyl 9-oxo-15-hydroxy-                                                      5-cis-prostenoate                                     567       511           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-19,20-dinor-                                                          prostanoate                                           568       512           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19,20-                                                           dinor-prostanoate                                     569       513           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-19,20-dinor-                                                            prostanoate                                           570       514           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-19,20-dinor-                                                         prostanoate                                           571       515           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-19,20-dinor-                                                         prostanoate                                           572       516           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-19,20-dinor-                                                         prostanoate                                           573       517           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19,20-dinor-                                                           prostanoate                                           574       518           Methyl 9-oxo-15-hdyroxy-                                                      19,20-dinor-5-cis-                                                            prostenoate                                           575       519           Ethyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                        576       520           Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-prostyno-                                                        ate                                                   577       521           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-prost-                                                       ynoate                                                578       522           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-prostynoate                                579       523           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-prost-                                                        ynoate                                                580       524           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-prostynoate                                  581       525           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-prostynoate                                  582       526           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-prostynoate                               583       527           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-prostynoate                                584       528           Ethyl-9-oxo-15-hydroxy-                                                       2-phenyl-16-prostynoate                               585       529           Butyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                        586       530           Isopropyl 9-oxo-15-hy-                                                        droxy-16-prostynoate                                  587       531           Methyl 9-oxo-15-hydroxy-                                                      16-prostynoate                                        588       532           Decyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                        589       533           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-prostynoate                               590       534           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-prostynoate                                 591       535           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-prostynoate                               592       536           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-                                                            prostynoate                                           593       537           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-                                                            prostynoate                                           594       538           Methyl 9-oxo-15-hydroxy-                                                      16-yne-5-cis-prostenoate                              595       539           Ethyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                    596       540           Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-cis-pros-                                                        tenoate                                               597       541           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-cis-                                                         prostenoate                                           598       542           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-cis-prosteno-                                                      ate                                                   599       543           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-cis-                                                          prostenoate                                           600       544           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-cis-prostenoate                              601       545           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-cis-prostenoate                              602       546           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-cis-prosten-                                                      oate                                                  603       547           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-cis-prosten-                                                       oate                                                  604       548           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-cis-prosten-                                                      oate                                                  605       549           Butyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                    606       550           Isopropyl 9-oxo-15-hy-                                                        droxy-16-cis-prostenoate                              607       551           Methyl 9-oxo-15-hydroxy-                                                      16-cis-prostenoate                                    608       552           Decyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                    609       553           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-cis-pros-                                                         tenoate                                               610       554           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-cis-prosteno-                                                       ate                                                   611       555           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-cis-pros-                                                         tenoate                                               612       556           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-cis-                                                        prostenoate                                           613       557           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-cis-                                                        prostenoate                                           614       558           Methyl 9-oxo-15-hydroxy-                                                      5-cis-16-cis-prostadi-                                                        enoate                                                ______________________________________                                    

EXAMPLES 615-662

Saponification of the 9-oxo-15-hydroxy alkyl esters designated in thetable below by the procedure described in Example 495 is productive ofthe carboxylic acids of the table.

                  TABLE 8                                                         ______________________________________                                               Starting alkyl                                                         Ex-    ester of     Product 9-oxo-15-hydroxy-                                 ample  Example      prostanoic acid                                           ______________________________________                                        615    559          9-oxo-15-hydroxy-2-ethyl-                                                     prostanoic acid                                           616    560          9-oxo-15-hydroxy-3,3-di-                                                      methyl-prostanoic acid                                    617    561          9-oxo-15-hydroxy-3-oxa-                                                       prostanoic acid                                           618    562          9-oxo-15-hydroxy-2-fluoro-                                                    prostanoic acid                                           619    563          9-oxo-15-hydroxy-2-phenyl-                                                    prostanoic acid                                           620    564          9-oxo-15-hydroxy-2-methyl-                                                    prostanoic acid                                           621    565          9-oxo-15-hydroxy-3-thia-                                                      prostanoic acid                                           622    566          9-oxo-15-hydroxy-5-cis-                                                       prostanoic acid                                           623    567          9-oxo-15-hydroxy-2-ethyl-                                                     19,20-dinor-prostanoic                                                        acid                                                      624    568          9-oxo-15-3,3-dimethyl-19,                                                     20-dinor-prostanoic acid                                  625    569          9-oxo-15-hydroxy-3-oxa-                                                       19,20-dinor-prostanoic                                                        acid                                                      626    570          9-oxo-15-hydroxy-2-fluoro-                                                    19,20-dinor-prostanoic                                                        acid                                                      627    571          9-oxo-15-hydroxy-2-phenyl-                                                    19,20-dinor-prostanoic                                                        acid                                                      628    572          9-oxo-15-hydroxy-2-methyl-                                                    19,20-dinor-prostanoic                                                        acid                                                      629    573          9-oxo-15-hydroxy-3-thia-                                                      19,20-dinor-prostanoic                                                        acid                                                      630    574          9-oxo-15-hydroxy-19,20-                                                       dinor-cis-prostenoic acid                                 631    575          9-oxo-15-hydroxy-16-pros-                                                     tynoic acid                                               632    576          9-oxo-15-hydroxy-6,7-dinor-                                                   16-prostynoic acid                                        633    577          9-oxo-15-hydroxy-7a,7b-bis-                                                   homo-16-prostynoic acid                                   634    578          9-oxo-15-hydroxy-2-ethyl-                                                     16-prostynoic acid                                        635    579          9-oxo-15-hydroxy-3,3-di-                                                      methyl-16-prostynoic acid                                 636    580          9-oxo-15-hydroxy-3-oxa-16-                                                    prostynoic acid                                           637    581          9-oxo-15-hydroxy-7-nor-16-                                                    prostynoic acid                                           638    582          9-oxo-15-hydroxy-2-fluoro-                                                    16-prostynoic acid                                        639    583          9-oxo-15-hydroxy-7a-homo-                                                     16-prostynoic acid                                        640    584          9-oxo-15-hydroxy-2-phenyl-                                                    16-prostynoic acid                                        641    589          9-oxo-15-hydroxy-2-methyl-                                                    16-prostynoic acid                                        642    590          9-oxo-15-hydroxy-3-thia-                                                      16-prostynoic acid                                        643    591          9-oxo-15-hydroxy-10a-homo-                                                    16-prostynoic acid                                        644    592          9-oxo-15-hydroxy-10a-homo-                                                    7-nor-16-prostynoic acid                                  645    593          9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-prostynoic acid                                646    594          9-oxo-15-hydroxy-16-yne-5-                                                    cis-prostenoic acid                                       647    595          9-oxo-15-hydroxy-16-cis-                                                      prostenoic acid                                           648    596          9-oxo-15-hydroxy-6,7-dinor-                                                   16-cis-prostenoic acid                                    649    597          9-oxo-15-hydroxy-7a,7b-bis-                                                   homo-16-cis-prestenoic acid                               650    598          9-oxo-15-hydroxy-2-ethyl-                                                     16-cis-prostenoic acid                                    651    599          9-oxo-15-hydroxy-3,3-di-                                                      methyl-16-cis-prostenoic                                                      acid                                                      652    600          9-oxo-15-hydroxy-3-oxa-16-                                                    cis-prostenoic acid                                       653    601          9-oxo-15-hydroxy-7-nor-16-                                                    cis-prostenoic acid                                       654    602          9-oxo-15-hydroxy-2-fluoro-                                                    16-cis-prostenoic acid                                    655    603          9-oxo-15-hydroxy-7a-homo-                                                     16-cis-prostenoic acid                                    656    604          9-oxo-15-hydroxy-2-phenyl-                                                    16-cis-prostenoic acid                                    657    609          9-oxo-15-hydroxy-2-methyl-                                                    16-cis-prostenoic acid                                    658    610          9-oxo-15-hydroxy-3-thia-                                                      16-cis-prostenoic acid                                    659    611          9-oxo-15-hydroxy-10a-homo-                                                    16-cis-prostenoic acid                                    660    612          9-oxo-15-hydroxy-10a-homo-                                                    7-nor-16-cis-prostenoic                                                       acid                                                      661    613          9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-cis-prosten-                                                       oic acid                                                  662    614          9-oxo-15-hydroxy-5-cis-                                                       16-cis-prostadienoic                                                          acid                                                      ______________________________________                                    

EXAMPLE 663 Ethyl 9-oxo-15-hydroxy-16-trans-prostenoate

To a mixture of 1 g. of ethyl 9-oxo-15-hydroxy-16-prostynoate (Example575), 11 ml. of water and 27 ml. of dimethylformamide is added 27 ml. of0.45 M chromous sulfate solution. The mixture is stirred for 48 hoursunder nitrogen atmosphere. The mixture then is extracted with etherseveral times and the combined extracts are taken to dryness. Silica gelchromatography gives the subject product as an oil.

EXAMPLES 664-682

Treatment of the 9-oxo-15-hydroxy-16-prostynoates listed in Table 8Abelow with chromous sulfate in the manner of Example 663 is productiveof the product 9-oxo-15-hydroxy-16-trans-prostenoates of the table.

                  TABLE 8A                                                        ______________________________________                                                  Starting      Product                                               Ex-       16-prostenoate                                                                              9-oxo-15-hydroxy-16-                                  ample     of Example    trans-prostenoate                                     ______________________________________                                        664       576           Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-trans-                                                           prostenoate                                           665       577           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-trans-                                                       prostenoate                                           666       578           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-trans-pros-                                                        tenoate                                               667       579           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-trans-                                                        prostenoate                                           668       580           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-trans-prosten-                                                       oate                                                  669       581           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-trans-pros-                                                          tenoate                                               670       582           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-trans-pros-                                                       tenoate                                               671       583           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-trans-pros-                                                        tenoate                                               672       584           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-trans-pros-                                                       tenoate                                               673       585           Butyl 9-oxo-15-hydroxy-                                                       16-trans-prostenoate                                  674       586           Isopropyl 9-oxo-15-                                                           hydroxy-16-trans-pros-                                                        tenoate                                               675       587           Methyl-9-oxo-15-hydroxy-                                                      16-trans-prostenoate                                  676       588           Decyl 9-oxo-15-hydroxy-                                                       16-trans-prostenoate                                  677       589           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-trans-pros-                                                       tenoate                                               678       590           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-trans-pros-                                                         tenoate                                               679       591           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-trans-pros-                                                       tenoate                                               680       592           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-trans-                                                      prostanoate                                           681       593           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-trans-                                                      prostenoate                                           682       594           Methyl 9-oxo-15-hydroxy-                                                      5-cis,16-trans-prosta-                                                        dienoate                                              ______________________________________                                    

EXAMPLES 683-689

Saponification of the alkyl 9-oxo-15-hydroxy-16-trans-prostenoateslisted in Table 8B below by the procedure described in Example 495 isproductive of the corresponding prostenoic acids of the table.

                  TABLE 8B                                                        ______________________________________                                              Starting      Product 9-oxo-15-                                         Ex-   alkyl ester   hydroxy-16-trans-                                         ample of Example    prostenoic acids                                          ______________________________________                                        683   663           9-oxo-15-hydroxy-16-                                                          trans-prostenoic acid                                     684   664           9-oxo-15-hydroxy-6,7-                                                         dinor-16-trans-prosten-                                                       oic acid                                                  685   665           9-oxo-15-hydroxy-7a,7b-                                                       bishomo-16-trans-pros-                                                        tenoic acid                                               686   666           9-oxo-15-hydroxy-2-                                                           ethyl-16-trans-prosten-                                                       oic acid                                                  687   667           9-oxo-15-hydroxy-3,3-                                                         dimethyl-16-trans-pros-                                                       tenoic acid                                               688   668           9-oxo-15-hydroxy-3-oxa-                                                       16-trans-prostenoic acid                                  689   669           9-oxo-15-hydroxy-7-nor-                                                       16-trans-prostenoic acid                                  690   670           9-oxo-15-hydroxy-2-                                                           fluoro-16-trans-pros-                                                         tenoic acid                                               691   671           9-oxo-15-hydroxy-7a-                                                          homo-16-trans-prostenoic                                                      acid                                                      692   672           9-oxo-15-hydroxy-2-                                                           phenyl-16-trans-pros-                                                         tenoic acid                                               693   677           9-oxo-15-hydroxy-2-meth-                                                      yl-16-trans-prostenoic                                                        acid                                                      694   678           9-oxo-15-hydroxy-3-thia-                                                      16-trans-prostenoic acid                                  695   679           9-oxo-15-hydroxy-102-                                                         homo-16-trans-prostenoic                                                      acid                                                      696   680           9-oxo-15-hydroxy-10a-                                                         homo-7-nor-16-trans-                                                          prostenoic acid                                           697   681           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-trans-pro-                                                         stenoic acid                                              698   682           9-oxo-15-hydroxy-5-cis,                                                       16-trans-prostadienoic                                                        acid                                                      ______________________________________                                    

EXAMPLE 699 Preparation of 9-oxo-15-hydroxy-3,3-dimethylprostanoic acid

A 2 g. sample of 9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoic acidis hydrogenated using 700 mg. of 10% palladium on carbon in 50 ml. ofabsolute alcohol. The catalyst is removed by filtration and the motherliquor is taken to dryness to give 2 of subject compound as an oil.

EXAMPLE 723 Preparation of 1-chloro-trans-1-octen-3-one

To a slurry of 233.5 g. (1.75 moles) of aluminum chloride in 390 ml. ofcarbon tetrachloride, saturated with acetylene and cooled in an icebath, is added over 20 minutes 201.9 g. (1.50 moles) of hexanoylchloride. After the addition is complete, acetylene is bubbled into themixture as rapidly as it is absorbed and for 1 hour after absorptionbecomes slow. The mixture is poured onto 1700 g. of ice and 720 ml. ofsaturated brine. The organic phase is separated and the aqueous phase iswashed with ether. The combined organic phase and washings are washedwith saturated brine, dried (Na₂ SO₄) and evaporated. The residual oilis combined with 10 g. of hydroquinone and distilled to yield acolorless oil, b.p. 51°-52° C. (0.10 torr).

EXAMPLE 724 Preparation of 1-iodo-trans-1-octen-3-one

A mixture of 54.5 g. (0.364 mole) of sodium iodide and 40 g. (0.249mole) of 1-chloro-trans-1-octen 3-one (Example 723) in 360 ml. ofacetone is stirred and refluxed for 24 hours. The reaction mixture iscooled, filtered and concentrated. The residue is partitioned betweenwater and ether. The organic phase is washed with dilute sodiumbicarbonate solution, brine, dried (MgSO₄) and evaporated to an oil.This material is used directly without purification.

EXAMPLE 725 Preparation of 1-bromo-trans-1-octen-3 one

A mixture of 68.0 g. (0.424 mole) of 1-chloro-trans-1-octen-3 one(Example 723) and 444 g. (4.24 moles) of anhydrous lithium bromide in900 ml. of 2-pentanone is refluxed for 30 minutes, cooled, andpartitioned between ice water and ether. The organic phase is washedwith water and saturated brine, dried (NaSO₄), and evaporated to an oil.This material is used directly without purification.

EXAMPLE 726 Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 14.29 g. (0.378 mole) of sodium borohydridein 400 ml. of anhydrous ethanol is added the crude1-bromo-trans-1-octen-3-one (Example 725), from 0.424 mole of1-chloro-trans-1-octen-3-one) over 30 minutes. The mixture is stirredfor 2 hours with ice cooling and is then partitioned between ice waterand benzene. The organic phase is washed with water and saturated brine,dried (Na₃ SO₄), and evaporated to an oil. Fractional distillationyields the title compound as a colorless oil, b.p. 66°-68° C. (0.025torr).

EXAMPLE 727 Preparation of 1-chloro-trans-1-octen-3-ol

Treatment of 1-chloro-trans-1-octen-3-one (Example 723) with sodiumborohydride in the manner of Example 726 is productive of the subjectcompound.

EXAMPLE 728 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-octene

A mixture of 6.212 g. (0.030 mole) of 1-bromo-trans-1-octen-3-ol(Example 726) and 10.67 g. (0.033 mole) of triphenylmethyl bromide in 40ml. of pyridine is heated to 100° C. for 1.5 hours under an inertatmosphere. The mixture is cooled and filtered. The filtrate ispartitioned between ice water and ether. The organic phase is washedwith cold dilute hydrochloric acid, saturated sodium bicarbonatesolution, and saturated brine, dried (NaSO₄), and evaporated to an oil.The latter is dissolved in hexane and passed through 250 g. of Florisil®to yield after evaporation a colorless oil. Found for Ca₇ Ha₉ OBr:C,72.13; H, 6.61; Br. 17.57.

EXAMPLE 729 Preparation of 1-iodo-trans-1-octen-3-ol

Treatment of 63 g. (0.25 mole) of 1-iodo-trans-1-octen-3one (Example724) with sodium borohydride in the manner described in Example 726 gave58 g. of yellow oil. The oil is purified by adsorption chromatography ona magnesia silica gel column using benzene as eluent to give a lightyellow oil.

EXAMPLE 730 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 7.62 g. (0.03 mole) of 1-iodo-trans-1-octen-3-ol with 10.67g. (0.033 mole) of triphenylmethyl bromide in pyridine in the mannerdescribed in Example 728 gave 13.448 g. (90%) of a colorless oil.

EXAMPLE 731 Preparation of 1-chloro-3-triphenylmethoxy-trans-1-octene

Treatment of 1-chloro-trans-1-octen-3-ol (Example 727) withtriphenylmethyl chloride by the method described in Example 728 exceptthat the heating period is extended to six hours provides the subjectcompound.

EXAMPLE 732 Preparation of 11-deoxy-prostaglandin-E, methyl ester andmethyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.535 g. (0.022 g. atom) of magnesium in 6 ml. oftetrahydrofuran is added under an inert atmosphere 2 ml. of a solutionof 6.548 g. (0.01455 mole) of 1-bromo-3 -trityloxy-trans-1-octene(Example 728) in 8 ml. of tetrahydrofuran. Reaction is initiated bywarming the mixture to 45° C. and adding 1 drop of methyl iodide. Theremainder of the halide is added at a rate to maintain a temperature of43°-46° C. and the mixture is heated at 45° C. for 1 hour after completeaddition of the halide. The Grignard reagent is cooled and added to anice cooled solution of 2.615 g. (0.0117 mole) of 2-(6-carbomethoxyhexyl)2-cyclopentenone (Example 83) and 0.229 g. of Copper (I)iodide-tri-in-butylphosphine in 6 ml. of ether over 6 minutes. Themixture is stirred with ice cooling for 30 minutes and poured into 200ml. of saturated ammonium chloride. The mixture is extracted into etherand the organic phase is washed with water and saturated brine, dried(NaSO₄) and evaporated. The residual oil is heated to 80° C. for 30minutes with 80% aqueous acetic acid under an inert atmosphere. Thismixture is cooled, evaporated to dryness, and the residue is separatedby dry column chromatography on silica gel using benzene-ethyl acetate4:1 as eluent. The title compounds are isolated as oils with Δ13 trans/Δ13 cis in ratio of 10:1. Complete resolution is effected with partitionchromatography [for a description see N.J. Weiss et al., Tetrahedron,20, 357 (1964)] on acid-washed Celite -545 using heptane: acetonitrile(Hold Back Volume-1000 ml.); 11-deoxy-prostaglandin-E₁ methyl ester isobtained in Hold Back Volume 3-5 and methyl15-hydroxy-9-oxo-13-cis-prostenoate is obtained in Hold Back Volume 6-8.

EXAMPLE 733 Preparation of 11-deoxy-prostaglandin-E₁ methyl ester andmethyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.243 g. (0.010 g. atom) of magnesium in 4 ml. oftetrahydrofuran is added under an inert atmosphere 2 ml. of a solutionof 4.494 g. (0.010 mole) of 1-bromo-3-trityloxy-trans-1-octene in 4 ml.of tetrahydrofuran. Reaction is initiated by warming the mixture to 65°C. and adding 1 drop of methyl iodide. The remainder of the halide isadded at a rate to maintain a temperature of 65°-70° C. and the mixtureis heated at 75°-80° C. for 30 minutes after complete addition of thehalide. The Grignard reagent is cooled and added to 2.243 g. (0.010mole) of 2-(6-carbomethoxyhexyl)-2-cyclopentenone and 0.200 g. of copper(I) iodide-tri-n-butylphosphine in 6 ml. of ether and worked up withsaturated ammonium chloride solution and aqueous acetic acid in themanner of Example 121. The products are isolated as described in Example732 to yield 11-deoxy-prostaglandin E₁ methyl ester and methyl15-hydroxy-9-oxo-13-cis-prostenoate in a ratio of 2:1.

EXAMPLE 734 Preparation of 15-hydroxy-9-oxo-cis-prostenoic acid

Methyl 15-hydroxy-9-oxo-cis-prostenoic acid is treated with potassiumhydroxide in aqueous methanol and worked up as described in Example 495to yield the title compound, m.p. 71°-75° C.

EXAMPLE 735 Preparation of Prostaglandin-E₁ and9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

A Grignard reagent is prepared as described in Example 732 from 0.535 g.(0.022 g. atom) of magnesium, 6.742 g. (0.015 mole) of1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 11 ml. oftetrahydrofuran at a temperature of 40°-42° C. The Grignard reagent isadded to 3.95 g. of2-(6-carbotetrahydropyranyloxyhexyl)-4-tetrahydropyroxyloxy-2-cyclopentenone(Example 95) and 0.589 g. of copper (I) iodide tri-n-butylphosphine in10 ml. of tetrahydrofuran and is worked up with ammonium chloride asdescribed in Example 732. The protecting groups are removed by treatingthe worked up material, as described in Example 121, with 320 mol ofacetic acid-water-tetrahydrofuran 2:1:1 at 45° C. and the products areisolated by chromatography on silica gel with a benzene-ethyl acetategradient and resolved via partition chromatography on acid-washed Celite545.

EXAMPLE 736 Preparation of Prostaglandin-E₁, and9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

Treatment of2-(6-carbotetrahydropyranylhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone(Example 95) with the Grignard reagent prepared from1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) in the presenceof Copper (I) iodide tri-n-butylphosphine complex by the proceduredescribed in Example 733 is productive of the subject compounds.

EXAMPLE 737 Preparation of 9m,15-dihydroxy-13-trans-prostenoic acid

To a solution of 453 mg. of 9-oxo-15-hydroxy-13-trans-prostenoic acid in4.5 ml. of tetrahydrofuran, stirred in an ice bath under nitrogenatmosphere, is added dropwise 3.7 ml. of 0.76 M lithiumperhydro-9b-boraphenalylhydride. After 40 minutes at 0° C. there isadded 1.62 ml. of 38 sodium hydroxide followed by 1.62 ml. of 30%hydrogen peroxide. Ether is added and the resulting solution isacidified with 2 N hydrochloric acid. The ether layer is washed severaltimes with saturated sodium chloride solution, dried with anhydrousmagnesium sulfate and taken to dryness to give the subject product as anoil.

EXAMPLES 738-893

Treatment of the 9-oxo derivatives designated in the table below withlithium perhydro-9α-borophenalyl hydride by the procedure described inExample 737 provides the 9α,13-dihydroxy derivatives of the table.

                  TABLE 9                                                         ______________________________________                                              Starting 9-oxo-                                                         Ex-   derivative of                                                                             Product 9α,15-Dihydroxy                               ample Example     Derivative                                                  ______________________________________                                        738   375         9α,15-dihydroxy-5,6,7-                                                  trinor-13-trans-prosten-                                                      oic acid                                                    739   376         9α,15-dihydroxy-7a,7b-                                                  bishomo-13-trans-pros-                                                        tenoic acid                                                 740   377         9α,15-dihydroxy-2-ethyl-                                                13-trans-prostenoic                                                           acid                                                        741   378         9α,15-dihydroxy-3,3-di-                                                 methyl-13-trans-prosten-                                                      oic acid                                                    742   379         9α,14-dihydroxy-3-oxo-                                                  13-trans-prostenoic                                                           acid                                                        743   380         9α,15-dihydroxy-7-nor-                                                  13-trans-prostenoic                                                           acid                                                        744   381         9α,15-dihydroxy-2-fluoro-                                               13-trans-prostenoic acid                                    745   382         9α,15-dihydroxy-7a-homo-                                                13-trans-prostenoic acid                                    746   383         9α,15-dihydroxy-2-phenyl-                                               13-trans-prostenoic acid                                    747   384         9α,15-dihydroxy-2-methyl-                                               13-trans-prostenoic acid                                    748   385         9α,15-dihydroxy-10a-homo-                                               13-trans-prostenoic acid                                    749   386         9α,15-dihydroxy-10a-homo-                                               5,6,7-trinor-13-trans-                                                        prostenoic acid                                             750   387         9α,15-dihydroxy-10a-homo-                                               7-nor-13-trans-prosten-                                                       oic acid                                                    751   388         9α,15-dihydroxy-7a,10-                                                  bishomo-13-trans-pros-                                                        tenoic acid                                                 752   389         9α,15-dihydroxy-3-thia-                                                 13-trans-prostenoic                                                           acid                                                        753   390         9α,15-dihydroxy-13-trans-                                               prostenoic acid                                             754   391         9α,15-dihydroxy-13-trans-                                               prostenoic acid                                             755   392         9α,15-dihydroxy-13-trans-                                               prostenoic acid                                             756   393         9α,15-dihydroxy-13-trans-                                               prostenoic acid                                             757   394         9α,15-dihydroxy-5-cis,13-                                               trans-prostadienoic acid                                    758   395         9α,15-dihydroxy-20-nor-                                                 13-trans-prostenoic acid                                    759   396         9α,15-dihydroxy-20-meth-                                                yl-13-trans-prostenoic                                                        acid                                                        760   397         9α,15-dihydroxy-16-ethyl-                                               13-trans-prostenoic acid                                    761   398         9α,15-dihydroxy-16-meth-                                                yl-20-nor-13-trans-pros-                                                      tenoic acid                                                 762   399         9α,15-dihydroxy-19-meth-                                                yl-13-trans, 18-prosta-                                                       dienoic acid                                                763   400         9α,15-dihydroxy-18,19-di-                                               methyl-13-trans, 18-pros-                                                     tadienoic acid                                              764   401         9α,15-dihydroxy-13-trans,                                               17-cis-prostadienoic acid                                   765   402         9α,15-dihydroxy-5,6,7-                                                  trinor-13-trans, 17-cis-                                                      prostadienoic acid                                          766   403         9α,15-dihydroxy-6,7-di-                                                 nor-13-trans, 17-cis-                                                         prostadienoic acid                                          767   404         9α,15-dihydroxy-7a,7b-                                                  bishomo-13-trans, 17-                                                         cis-prostadienoic acid                                      768   405         9α,15-dihydroxy-2-ethyl-                                                13-trans, 17-cis-pros-                                                        tadienoic acid                                              769   406         9α,15-dihydroxy-3,3-di-                                                 methyl-13-trans, 17-cis-                                                      prostadienoic acid                                          770   407         9α,15-dihydroxy-3-oxa-                                                  13-trans, 17-cis-pros-                                                        tadienoic acid                                              771   408         9α,15-dihydroxy-7-nor-                                                  13-trans, 17-cis-pros-                                                        tadienoic acid                                              772   409         9α,15-dihydroxy-2-fluoro-                                               13-trans, 17-cis-pros-                                                        tadienoic acid                                              773   410         9α,15-dihydroxy-7a-homo-                                                13-trans, 17-cis-pros-                                                        tadienoic acid                                              774   411         9α,15-dihydroxy-2-phen-                                                 yl-13-trans, 17-cis-                                                          prostadienoic acid                                          775   412         9α,15-dihydroxy-2-meth-                                                 yl-13-trans, 17-cis-                                                          prostadienoic acid                                          776   413         9α,15-dihydroxy-10a-ho-                                                 mo-13-trans, 17-cis-                                                          prostadienoic acid                                          777   414         9α,15-dihydroxy-10a-ho-                                                 mo-5,6,7-trinor-13-                                                           trans, 17-cis-prostadi-                                                       enoic acid                                                  778   415         9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-13-trans, 17-                                                        cis-prostadienoic acid                                      779   416         9α,15-dihydroxy-7a,10a-                                                 bishomo-13-trans, 17-                                                         cis-prostadienoic acid                                      780   417         9α,15-dihydroxy-3-thia-                                                 13-trans, 17-cis-pros-                                                        tadienoic acid                                              781   418         9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                                  782   419         9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                                  783   420         9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                                  784   421         9α,15-dihydroxy-13-trans,                                               17-cis-prostadienoic acid                                   785   422         9α,15-dihydroxy-5,6,7-                                                  trinor-19-isobutyl-13-                                                        trans, 18-prostadien-                                                         oic acid                                                    786   423         9α,15-dihydroxy-5,6,7-                                                  19,20-pentanor-13-trans,                                                      17-prostadienoic acid                                       787   424         9α,15-dihydroxy-19,20-di-                                               nor-13-trans, 18-prosta-                                                      dienoic acid                                                788   425         9α,15-dihydroxy-17,20-di-                                               methyl-20-isopropenyl-13-                                                     trans-prostenoic acid                                       789   426         9α,15-dihydroxy-16-ethyl-                                               6,7,19,20-tetranor-13-                                                        trans-prostenoic acid                                       790   427         9α,15-dihydroxy-18,19-                                                  dimethyl-6,7-dinor-13-                                                        trans, 18-prostadienoic                                                       acid                                                        791   428         9α,15-dihydroxy-16-ethyl-                                               7a,7b-bishomo-13-trans-                                                       prostenoic acid                                             792   429         9α,15-dihydroxy-19-meth-                                                yl-7a,7b-bishomo-13-                                                          trans, 18-prostadienoic                                                       acid                                                        793   430         9α,15-dihydroxy-2-ethyl-                                                19,20-dinor-13-trans-                                                         prostenoic acid                                             794   431         9α,15-dihydroxy-2,20-di-                                                ethyl-13-trans-prosten-                                                       oic acid                                                    795   432         9α,15-dihydroxy-2-ethyl-                                                16-methyl-20-nor-13-                                                          trans-prostenoic acid                                       796   433         9α,15-dihydroxy-2-ethyl-                                                18,19-dimethyl-13-                                                            trans, 18-prostadienoic                                                       acid                                                        797   434         9α,15-dihydroxy-3,3-di-                                                 methyl-18,19,20-trinor-                                                       13-trans-prostenoic                                                           acid                                                        798   435         9α,15-dihydroxy-3,3,20-                                                 trimethyl-13-trans-                                                           prostenoic acid                                             799   436         9α,15-dihydroxy-3,3,16-                                                 trimethyl-20-nor-13-                                                          trans-prostenoic acid                                       800   437         9α,15-dihydroxy-3,3-di-                                                 methyl-19-isobutyl-13-                                                        trans, 18-prostadienoic                                                       acid                                                        601   438         9α,15-dihydroxy-3,3-di-                                                 methyl-19,20-dinor-13-                                                        trans, 17-prostadienoic                                                       acid                                                        802   439         9α,15-dihydroxy-3-oxa-20-                                               nor-13-trans-prostenoic                                                       acid                                                        803   440         9α,15-dihydroxy-3-oxa-20-                                               methyl-13-trans-prosten-                                                      oic acid                                                    804   441         9α,15-dihydroxy-3-oxa-16-                                               ethyl-15-trans-prosten-                                                       oic acid                                                    805   142         9α,15-dihydroxy-3-oxa-16-                                               methyl-20-nor-13-trans-                                                       prostenoic acid                                             806   443         9α,15-dihydroxy-3-oxa-                                                  19,20-dinor-13-trans, 17-                                                     prostadienoic acid                                          807   444         9α,15-dihydroxy-7,19,20-                                                trinor-13-trans, 17-                                                          prostadienoic acid                                          808   445         9α,15-dihydroxy-7-nor-                                                  18,19-dimethyl-13-trans,                                                      18,prostadienoic acid                                       809   446         9α,15-dihydroxy-7,18,19,-                                               20-tetranor-16-methyl-13-                                                     trans-prostenoic acid                                       810   447         9α,15-dihydroxy-2-fluoro-                                               20-nor-13-trans-prosten-                                                      oic acid                                                    811   448         9α,15-dihydroxy-2-fluoro-                                               20-ethyl-13-trans-pros-                                                       tenoic acid                                                 812   449         9α,15-dihydroxy-2-fluoro-                                               16-ethyl-19,20-dinor-13-                                                      trans-prostenoic acid                                       813   450         9α,15-dihydroxy-2-fluoro-                                               16-methyl-20-nor-13-                                                          trans-prostenoic acid                                       814   451         9α,15-dihydroxy-2-fluoro-                                               19-methyl-13-trans, 18-                                                       prostadienoic acid                                          815   452         9α,15-dihydroxy-7a-homo-                                                18,19-dimethyl-13-trans,                                                      18-prostadienoic acid                                       816   453         9α,15-dihydroxy-7a-homo-                                                19,20-dinor-13-trans,                                                         17-prostadienoic acid                                       817   454         9α,15-dihydroxy-2-phenyl-                                               20-nor-13-trans-prosten-                                                      oic acid                                                    818   455         9α,15-dihydroxy-2-phenyl-                                               20-ethyl-13-trans-pros-                                                       tenoic acid                                                 819   456         9α,15-dihydroxy-2-phenyl-                                               16-ethyl-13-trans-pros-                                                       tenoic acid                                                 820   484         9α,15-dihydroxy-20-nor-5-                                               cis,13-trans-prostadi-                                                        enoic acid                                                  821   485         9α,15-dihydroxy-20-meth-                                                yl-5-cis, 13-trans-pros-                                                      tadienoic acid                                              822   486         9α,15-dihydroxy-16-ethyl-                                               5-cis, 13-trans-prosta-                                                       dienoc acid                                                 823   487         9α,15-dihydroxy-16-meth-                                                yl-20-nor-5-cis, 13-                                                          trans-prostadienoic                                                           acid                                                        824   488         9α,15-dihydroxy-19-meth-                                                yl-5-cis, 13-trans, 18-                                                       prostatrienoic acid                                         825   489         9α,15-dihydroxy-18,19-                                                  dimethyl-5-cis, 13-                                                           trans, 18-prostatrien-                                                        oic acid                                                    826   490         9α,15-dihydroxy-19,20-di-                                               nor-5-cis, 13-trans, 17-                                                      prostatrienoic acid                                         827   491         9α,15-dihydroxy-5-cis,-                                                 13-trans, 17-cis-prosta-                                                      trienoic acid                                               828   734         9α,15-dihydroxy-13-cis-                                                 prostenoic acid                                             829   735         9α,11α,15-trihydroxy-13-                                          cis-prostenoic acid                                         830   615         9α,15-dihydroxy-2-ethyl-                                                prostenoic acid                                             831   616         9α,15-dihydroxy-3,3-di-                                                 methyl-prostanoic acid                                      832   617         9α,15-dihydroxy-3-oxa-                                                  prostanoic acid                                             833   618         9α,15-dihydroxy-2-fluoro-                                               prostanoic acid                                             834   619         9α,15-dihydroxy-2-phenyl-                                               prostenoic acid                                             835   620         9α,15-dihydroxy-2-meth-                                                 yl-prostanoic acid                                          836   621         9α,15-dihydroxy-3-thia-                                                 prostanoic acid                                             837   622         9α,15-dihydroxy-5-cis-                                                  prostanoic acid                                             838   623         9α,15-dihydroxy-2-ethyl-                                                19,20-dinor-prostanoic                                                        acid                                                        839   624         9α,13-dihydroxy-3,3-di-                                                 methyl-19,20-dinor-pros-                                                      tanoic acid                                                 840   623         9α,15-dihydroxy-3-oxo-                                                  19,20-dinor-prostanoic                                                        acid                                                        841   626         9α,15-dihydroxy-2-fluoro-                                               19,20-dinor-prostanoic                                                        acid                                                        842   627         9α,15-dihydroxy-2-phenyl-                                               19,20-dinor-prostanoic                                                        acid                                                        843   628         9α,15-dihydroxy-2-meth-                                                 yl-19,20-dinor-prostan-                                                       oic acid                                                    844   629         9α,15-dihydroxy-3-thia-                                                 19,20-dinor-prostanoic                                                        acid                                                        845   630         9α,15-dihydroxy-19,20-di-                                               nor-5-cis-prostenoic acid                                   846   631         9α,15-dihydroxy-16-pros-                                                tynoic acid                                                 847   632         9α,15-dihydroxy-6,7-di-                                                 nor-16-prostynoic acid                                      848   633         9α,15-dihydroxy-7a,7b-                                                  bishomo-16-prostynoic                                                         acid                                                        849   634         9α,15-dihydroxy-2-ethyl-                                                16-prostynoic acid                                          850   635         9α,15-dihydroxy-3,3-di-                                                 methyl-16-prostynoic                                                          acid                                                        851   636         9α,15-dihydroxy-3-oxo-16-                                               prostynoic acid                                             852   637         9α,15-dihydroxy-7-nor-16-                                               prostynoic acid                                             853   638         9α,15-dihydroxy-2-fluoro-                                               16-prostynoic acid                                          854   639         9α,15-dihydroxy-7a-homo-                                                16-prostynoic acid                                          855   640         9α,15-dihydroxy-2-phenyl-                                               16-prostynoic acid                                          856   641         9α,15-dihydroxy-2-methyl-                                               16-prostynoic acid                                          857   642         9α,15-dihydroxy-3-thia-                                                 16-prostynoic acid                                          858   643         9α,15-dihydroxy-10a-ho-                                                 mo-16-prostynoic acid                                       859   644         9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-16-prostynoic                                                        acid                                                        860   645         9α,15-dihydroxy-7a,10a-                                                 bishomo-16-prostynoic                                                         acid                                                        861   646         9α,15-dihydroxy-16-yne-                                                 5-cis-prostenoic acid                                       862   683         9α,15-dihydroxy-16-trans-                                               prostenoic acid                                             863   684         9α,15-dihydroxy-6,7-di-                                                 nor-16-trans-prostenoic                                                       acid                                                        864   685         9α,15-dihydroxy-7a,7b-                                                  bishomo-16-trans-pros-                                                        tenoic acid                                                 865   686         9α,15-dihydroxy-2-ethyl-                                                16-trans-prostenoic acid                                    866   687         9α,15-dihydroxy-3,3-di-                                                 methyl-16-trans-prosten-                                                      oic acid                                                    867   688         9α,15-dihydroxy-3-oxa-16-                                               trans-prostenoic acid                                       868   689         9α,15-dihydroxy-7-nor-16-                                               trans-prostenoic acid                                       869   690         9α,15-dihydroxy-2-fluoro-                                               16-trans-prostenoic acid                                    870   691         9α,15-dihydroxy-7a-homo-                                                16-trans-prostenoic acid                                    871   692         9α,15-dihydroxy-2-phenyl-                                               16-trans-prostenoic acid                                    872   693         9α,15-dihydroxy-2-methyl-                                               16-trans-prostenoic acid                                    873   694         9α,15-dihydroxy-3-thia-                                                 16-trans-prostenoic acid                                    874   695         9α,15-dihydroxy-10a-homo-                                               16-trans-prostenoic acid                                    875   696         9α,15-dihydroxy-10-a-homo-                                              7-nor-16-trans-prosten-                                                       oic acid                                                    876   697         9α,15-dihydroxy-7a,10a-                                                 bishomo-16-trans-pros-                                                        tenoic acid                                                 877   698         9α,15-dihydroxy-5-cis,-                                                 16-trans-prostadienoic                                                        acid                                                        878   647         9α,15-dihydroxy-16-cis-                                                 prostenoic acid                                             879   648         9α,15-dihydroxy-6,7-di-                                                 nor-16-cis-prostenoic                                                         acid                                                        880   649         9α,15-dihydroxy-7a,7b-                                                  bishomo-16-cis-prosten-                                                       oic acid                                                    881   650         9α,15-dihydroxy-2-ethyl-                                                16-cis-prostenoic acid                                      882   651         9α,15-dihydroxy-3,3-di-                                                 methyl-16-cis-prosten-                                                        oic acid                                                    883   652         9α,15-dihydroxy-3-oxa-                                                  16-cis-prostenoic acid                                      884   653         9α,15-dihydroxy-7-nor-                                                  16-cis-prostenoic acid                                      885   654         9α,15-dihydroxy-2-fluoro-                                               16-cis-prostenoic acid                                      886   655         9α,15-dihydroxy-7a-homo-                                                16-cis-prostenoic acid                                      887   656         9α,15-dihydroxy-2-phenyl-                                               16-cis-prostenoic acid                                      888   657         9α,15-dihydroxy-2-methyl-                                               16-cis-prostenoic acid                                      889   658         9α,15-dihydroxy-3-thia-                                                 16-cis-prostenoic acid                                      890   659         9α,15-dihydroxy-10a-ho-                                                 mo-16-cis-prostenoic                                                          acid                                                        891   660         9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-16-cis-prosten-                                                      oic acid                                                    892   661         9α,15-dihydroxy-7a,10a-                                                 bishomo-16-cis-prosten-                                                       oic acid                                                    893   662         9α,15-dihydroxy-5-cis,-                                                 16-cis-prostadienoic                                                          acid                                                        ______________________________________                                    

EXAMPLE 894 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(2-methoxyethyl)-cyclopentan-1-one

Treatment of 2-cyclopentanone carboxylate (mixed methyl and ethylesters) with 2-methoxyethyl bromide by the method of Example 1 furnishesthe subject compound as an oil, b.p. 90° C. (0.1 mm).

EXAMPLE 895 Preparation of 2-(2-methoxyethyl)cyclopentan-1-one

Heating 8 g. of 2-carboalkoxy(methyl/ethyl)2-(2-methoxyethyl)-cyclopentan-1-one (Example 894) in 8ml. of 20% aqueous hydrochloric acid at reflux for 3.5 hours andisolating the product by the method of Example 2 furnishes the subjectcompound as an oil, b.p. 45°-50° C. (0.02 mm).

EXAMPLE 896 Preparation of 1-acetoxy-2-(2-methoxyethyl)cyclopent-1-ene

The subject compound is prepared from2-(2-methoxyethyl)cyclopentan-1-one (Example 895) and acetic anhydrideby the procedure of Example 10. The product is an oil, b.p. 60° C. (0.2mm.)

EXAMPLE 897 Preparation of 2-(2-hydroxyethyl)-cyclopent-2-en-1-one

The enol acetate of Example 896 is brominated and dehydrobrominated bythe method described in Example 13. The crude product is then dissolvedin methylene chloride and is added at -78° C. to a methylene chloridesolution containing about seven molar equivalents of boron tribromide.After one hour at -78° C. the solution is allowed to warm to roomtemperature and is then kept at ambient temperatures for a total ofeighteen hours. The mixture is poured into water and extracted withether. The organic phase is washed with saturated saline solution, thenwater and is dried. Evaporation of solvents leaves subject product,which is purified by distillation. The combined organic phases arewashed with ice cold 5% sodium hydroxide solution, ice cold 5%hydrochloric acid, and saturated sodium chloride solution, dried withanhydrous magnesium sulfate and taken to dryness. Distillation gives apale yellow oil; λ max 5.85 μ (carbonyl group).

EXAMPLE 898 Preparation of 2-formylmethylcycopent-2-en-1-one

Chromium trioxide (0.6 mol) is added to a stirring solution of (1.2 mol)of anhydrous pyridine in 1500 ml. of anhydrous methylene chloride cooledin an ice bath. The deep red suspension is stirred for 15 minutes at 0°C. and 45 minutes at ambient temperature. A solution of 01.5 mol of2-(2-hydroxyethyl)-cyclopent-2-en-1-one (Example 897) in 50 ml. ofmethylene chloride is added, all at once, to the suspension. A blackterry deposit is formed immediately. After stirring the mixture for 25minutes at ambient temperature, the methylene chloride is decanted fromthe terry precipitate which is then triturated several times with ether.

EXAMPLE 899 Preparation of2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one

A mixture of 0.194 g. (0.007952 mole) of sodium hydride (free of mineraloil) and 5.5 ml. of dimethylsulfoxide is heated to 70° C. until gasevolution ceases under a nitrogen atmosphere. The resulting solution iscooled below room temperature and treated with a solution of 1.400 g.(0.00316 mole) of 4-carboxybutyltriphenyl phosphonium bromide [E. J.Corey et al., J. Am. Chem. Soc., 91, 5675 (1969)] in 6 ml. ofdimethylsulfoxide. To the resulting red solution is added 0.00263 moleof 2-formylmethylcyclopent-2-en-1-one (Example 898) in 2 ml. ofdimethylsulfoxide and the mixture is stirred at room temperature for2.25 hours. The mixture is poured into ice water, sodium hydroxidesolution is added to pH 12, and the neutral materials are extracted withdiethyl ether. The basic phase is acidified with dilute hydrochloricacid and is extracted with diethyl ether. The organic phase is washedwith water and saturated brine, dried (Na₂ SO₄), and evaporated to asemicrystalline mass. The latter is triturated with hot hexane, thesolids are filtered off, and the filtrate is evaporated to yield thesubject product as an oil.

EXAMPLE 900 Preparation of2-(6-carbomethoxy-2-cis-hexenyl)-cyclopent-2-en-1-one

Treatment of 2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one (Example899) with diazomethane in the usual manner is productive of the subjectester.

EXAMPLES 901-909

Hydrogenation of 13-trans-prostenoic acids designated in the table belowby the procedure of Example 699 is productive of the prostanoic acids ofthe table.

                  TABLE 10                                                        ______________________________________                                              Starting 13-                                                                  trans-pro-     Product                                                  Ex-   stenoic acid   Prostanoic                                               ample of Example     Acid                                                     ______________________________________                                        901   397            9-oxo-15-hydroxy-                                                             16-ethyl-pro-                                                                 stanoic acid                                             902   398            9-oxo-15-hydroxy-                                                             16-methyl-20-                                                                 nor-prostanoic                                                                acid                                                     903   400            9-oxo-15-hydroxy-                                                             18,19-dimethyl-                                                               prostanoic acid                                          904   426            9-oxo-15-hydroxy-                                                             16-ethyl-6,7,19,                                                              20-tetranor-pro-                                                              stanoic acid                                             905   428            9-oxo-15-hydroxy-                                                             16-ethyl-7a,7b-                                                               bishomo-prostan-                                                              oic acid                                                 906   429            9-oxo-15-hydroxy-                                                             19-methyl-7a,7b-                                                              bishomo-prostan-                                                              oic acid                                                 907   433            9-oxo-15-hydroxy-                                                             2-ethyl-18,19-                                                                dimethyl-pro-                                                                 stanoic acid                                             908   436            9-oxo-15-hydroxy-                                                             3,3,16-trimethyl-                                                             20-nor-prostanoic                                                             acid                                                     909   476            9-oxo-15-hydroxy-                                                             7a,10a,bishomo-16-                                                            methyl-20-nor-                                                                prostanoic acid                                          ______________________________________                                    

EXAMPLES 910-915

Treatment of the 9-oxo-alkyl esters designated in the table below withsodium borohydride by the procedure described in Example 257 isproductive of the corresponding 9-hydroxy derivative of the table. Theseproducts are obtained as 9α- and 9β-hydroxy eimeric mixtures.

                  TABLE 11                                                        ______________________________________                                              Starting 9-oxo                                                          Ex-   derivative of                                                                             Product                                                     ample Example     9α,9β-hydroxy derivative                         ______________________________________                                        910   260         ethyl 9α/9β,15-dihydroxy-                                          2-ethyl-13-trans-                                                             prostenoate                                                 911   261         ethyl 9α/9β,15-dihydroxy-                                          3,3-dimethyl-13-trans-                                                        prostenoate                                                 912   262         ethyl 9α/9β,15-dihydroxy-                                          3-oxa-13-trans-                                                               prostenoate                                                 913   266         ethyl 9α/9β,15-dihydroxy-                                          2-phenyl-13-trans-                                                            prostenoate                                                 914   272         ethyl 9α/9β,15-dihydroxy-                                          3-thia-13-trans-                                                              prostenoate                                                 915   284         ethyl 9α/9β,15-dihydroxy-                                          13-trans,17-cis-                                                              prostadienoate                                              ______________________________________                                    

EXAMPLES 916-921

Saponification of the ethyl esters designated in the table below by theprocedure described in Example 122 furnishes the carboxylic acids of thetable.

                  TABLE 12                                                        ______________________________________                                                          Product 9α/9β,15-di-                             Ex-   Starting ethyl                                                                            hydroxy-13-trans-pro-                                       ample of Example  stenoic acid                                                ______________________________________                                        916   910         9α/9β,15-dihydroxy-                                                2-ethyl-13-trans-                                                             prostenoic acid                                             917   911         9α/9β,15-dihydroxy-                                                3,3-dimethyl-13-                                                              trans-prostenoic                                                              acid                                                        918   912         9α/9β,15-dihydroxy-                                                3-oxa-13-trans-                                                               prostenoic acid                                             919   913         9α/9β,15-dihydroxy-                                                2-phenyl-13-trans-                                                            prostenoic acid                                             920   914         9α/9β,15-dihydroxy-                                                3-thia-13-trans-                                                              prostenoic acid                                             921   915         9α/9β,15-dihydroxy-                                                13-trans,17-cis-                                                              prostadienoic acid                                          ______________________________________                                    

EXAMPLES 922-932

Treatment of the cycloalkenones of Table 13, which follows, with theGrignard reagent, prepared from1-bromo-3-triphenylmethoxy-trans-1-octene and magnesium according to theprocedure of Example 733, hydrolizing theintermediate15-0-triphenylmethyl derivatives with glacial aceticacid-tetrahydrofura-water (4:2:1) according to the procedure of Example121, and isolating the products in the manner described in Example 732is productive of the product 9-oxo-15-hydroxy-13-cis-prostenoates and9-oxo-15-hydroxy-13-trans-prostenoates of the table.

                                      TABLE 13                                    __________________________________________________________________________          Starting cyclopentenone                                                                      Product 15-hydroxy-13-cis-                                                                         Product 15-hydroxy-13-trans-        Example                                                                             Ester of Example                                                                             prostenoate ester    prostenoate ester                   __________________________________________________________________________    922   23             ethyl 9-oxo-15-hydroxy-7a,7b-                                                                      ethyl 9-oxo-15-hydroxy-7a,7b-                            bishomo-13-cis-prostenoate                                                                         bishomo-13-trans-prostenoate        923   31             ethyl 9-oxo-15-hydroxy-2-ethyl-                                                                    ethyl 9-oxo-15-hdroxy-2-                                 13-cis-prostenoate   ethyl-13-trans-prostenoate          924   41             ethyl 9-oxo-15-hydroxy-3,3-di-                                                                     ethyl 9-oxo-15-hydroxy-3,3-di-                           methyl-13-cis-prostenoate                                                                          methyl 13-trans-prostenoate         925   46             ethyl 9-oxo-15-hydroxy-3-oxa-                                                                      ethyl 9-oxo-15-hydroxy-3-oxa-                            13-cis-prostenoate   13-trans-prostenoate                926   53             ethyl 9-oxo-15-hydroxy-7-nor-                                                                      ethyl 9-oxo-15-hydroxy-7-nor-                            13-cis-prostenoate   13-trans-prostenoate                927   70             ethyl 9-oxo-15-hydroxy-2-fluoro-                                                                   ethyl 9-oxo-15-hydroxy-2-                                13-cis-prostenoate   fluoro-13-trans-prostenoate         928   84             n-decyl 9-oxo-15-hydroxy-                                                                          n-decyl 9-oxo-15-hydroxy-                                13-cis-prostenoate   13-trans-prostenoate                929   99             ethyl 9-oxo-15-hydroxy-2-methyl-                                                                   ethyl 9-oxo-15-hydroxy-2-                                13-cis-prostenoate   methyl-13-trans-prostenoate         930   111            ethyl 9-oxo-15-hydroxy-10a-homo-                                                                   ethyl 9-oxo-15-hydroxy-10a-                              13-cis-prostenoate   homo-13-trans-prostenoate           931   118            ethyl 9-oxo-15-hydroxy-3-thia-                                                                     ethyl 9-oxo-15-hydroxy-3-                                13-cis-prostenoate   thia-13-trans-prostenoate           932   900            methyl 9-oxo-15-hydroxy-5-                                                                         methyl 9-oxo-15-hydroxy-5-                               cis, 13-cis-prostadienoate                                                                         cis, 13-trans-                                                                prostadienoate                      __________________________________________________________________________

EXAMPLES 933-942

Saponification of the 13-cis-prostenoate alkyl esters designated inTable 14 below by the method described in Example 122 is productive ofthe 13-cis-prostenoic acids of the Table.

                                      TABLE 14                                    __________________________________________________________________________          Starting 13-cis-prostenoate                                             Example                                                                             Ester of Example                                                                            Product 13-cis-prostenoic acids                           __________________________________________________________________________    933   922           9-oxo-15-hydroxy-7a,7b-bishomo-13-                                            cis-prostenoic acid                                       934   923           9-oxo-15-hydroxy-2-ethyl-13-cis-                                              prostenoic acid                                           935   924           9-oxo-15-hydroxy-3,3-dimethyl-13-cis-                                         prostenoic acid                                           936   925           9-oxo-15-hydroxy-3-oxa-13-cis-prostenoic acid             937   926           9-oxo-15-hydroxy-7-nor-13-cis-prostenoic acid             938   927           9-oxo-15-hydroxy-2-fluoro-13-cis-prostenoic acid          939   929           9-oxo-15-hydroxy-2-methyl-13-cis-prostenoic acid          940   930           9-oxo-15-hydroxy-10a-homo-13-cis-prostenoic acid          941   931           9-oxo-15-hydroxy-3-thia-13-cis-prostenoic acid            942   932           9-oxo-15-hydroxy-5-cis, 13-cis-prostadienoic              __________________________________________________________________________                        acid                                                  

EXAMPLES 943-954

Treatment of the 9-oxo-13-cis-prostenoic acids and esters of Table 15below with lithium perhydro-9b-boraphenalyl hydride by the proceduredescribed in Example 737 furnishes the 9α,15-dihydroxy-13-cis-prostenoicacids and esters of the table.

                                      TABLE 15                                    __________________________________________________________________________          Starting 9-oxo-13-cis-                                                        prostenoic derivative                                                   Example                                                                             of Example    Product 9α, 15-hydroxy-13-cis-prostenoic acid                           and esters                                                __________________________________________________________________________    943   933           9,15-dihydroxy-7a,7b-bishomo-13-cis-prostenoic acid       944   934           9,15-dihydroxy-2-ethyl-13-cis-prostenoic acid             945   935           9,15-dihydroxy-3,3-dimethyl-13-cis-prostenoic acid        946   936           9,15-dihydroxy-3-oxa-13-cis-prostenoic acid               947   937           9,15-dihydroxy-7-nor-13-cis-prostenoic acid               948   938           9,15-dihydroxy-2-fluoro-13-cis-prostenoic acid            949   939           9,15-dihydroxy-2-methyl-13-cis-prostenoic acid            950   940           9,15-dihydroxy-10a-homo-13-cis-prostenoic acid            951   941           9,15-dihydroxy-3-thia-13-cis-prostenoic acid              952   942           9,15-dihydroxy-5-cis,-13-cis-prostadienoic acid           953   932           methyl 9,15-dihydroxy-5-cis, 13-cis-prostadienoate        954   928           n-decyl 9,15-dihydroxy-13-cis-prostenoate                 __________________________________________________________________________

EXAMPLE 955 Preparation of 1-iodo-trans-1-octen-3-ol

A solution of 78.2 g. (0.310 moles) of 1-iodo-trans-1-octen-3-one(Example 724) in 150 ml. of absolute ethanol is added dropwise over 2hours to a slurry of 6.49 g. (0.172 moles) of sodium borohydride in 50ml. of absolute ethanol cooled in an ice bath. After the addition iscomplete, the mixture is stirred for 2 hours with ice cooling and isthen poured into 1 l. of water. The mixture is extracted into benzeneand the organic phase is washed with saturated brine, dried (Na₂ SO₄)and evaporated. The resulting oil is dissolved into 400 ml. of absoluteethanol and treated with 5 mole percent of p-carboxyphenylhydrazine at70° C. for 1.5 hours to remove residual ketone. The mixture is cooledand evaporated and the residue is dissolved into 400 ml. of ether and isfiltered. The filtrate is washed with dilute sodium bicarbonate solutionand saturated brine, dried (Na₂ SO₄), and evaporated to an oil. This oilis chromatographed upon 2 Kg. of Florisil® packed in hexane and theproduct is obtained upon elution with benzene Distillation of theproduct yields a colorless oil, b.p. 74°-76° C. (0.005 tor.).

EXAMPLE 956 Preparation of1-iodo-3-(p-anisyldiphenylmethoxy)-trans-2-octene

A mixture of 14.92 g. (0.0588 mole) of 1-iodo-trans-1-octen-3-ol(Example 955) and 18.2 g. (0.588 mole) of p-anisyldiphenylmethylchloride in 165 ml. of dry pyridine is heated at 60° C. for 18 hoursunder an inert atmosphere. The mixture is cooled and the solvent isevaporated in vacuo. The residue is partitioned between ether and water,and the organic phase is washed with water and saturated brine, dried(MgSO₄), and evaporated. The residue is chromatographed upon 300 g. ofFlorisil® packed in hexane and the product is eluted with hexane and 4:1hexane-benzene the yield a colorless oil.

EXAMPLE 957 Preparation of methyl esters of dl-11-deoxyprostaglandin-E₁and dl-11-deoxy-15-epi-prostaglandin E₁

To a solution of 6.030 g. (0.01215 mole) of1-iodo-3-triphenylmethoxy-trans-1-octene (Example 730) in 8 ml. oftoluene cooled to -78° C. under an inert atmosphere is added 5.2 ml. ofa 2.34 M solution of n-butyllithium in hexane. The resulting solution isallowed to warm to -40° C. and is maintained at this temperature for 1hour. To the solution containing3-triphenylmethoxy-trans-1-octenyllithium is then added 5.0 ml. of a2.44 M (0.0122 mole) solution of trimethylaluminum in heptane and themixture is allowed to warm to -10° C. The mixture containing lithiumtrimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate is then cooled to-78° C. and to it is added a solution of 2.725 g. (0.01215 mole) of2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example 83) dissolved in 10ml. of diethyl ether. The mixture is allowed to warm to room temperatureand is stirred at ambient temperature for 18 hours. The mixture is thenpoured onto ice and diluted hydrochloric acid and is extracted intoether. The organic phase is washed with water and saturated brine, dried(Na₂ SO₄), and evaporated to yield a colorless oil. This oil is heatedwith 100 ml. of 80% aqueous acetic acid at 80° C. for 1 hour under aninert atmosphere. The resulting mixture is cooled and evaporated invacuo to dryness with 100 ml. of xylene to yield an oil. This oil isdry-column-chromatographed upon 400 g. of silica gel using 4:1benzene-ethyl acetate as eluent to yield a total of 2.59 g. ofdl-11-deoxyprostaglandin E₁ and dl-11-deoxy-15-epi-prostaglandin E₁methyl esters.

EXAMPLE 958 Preparation of4-(trimethylsiloxy)-2-(6-carbotrimethylsiloxyhexyl)cyclopent-2-en-1-one

To a solution of 5 g. of2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one (Example 94) in 10 ml.of dry N,N-dimethylformamide is added 5.4 g. of trimethylsilyl chloridein a nitrogen atmosphere. To the resulting solution cooled in a tapwater bath is added 5.05 g. of triethylamine in 10 ml. ofN,N-dimethylformamide dropwise. The resulting mixture is stirred at 60°C. in an oil-bath for 2 hours, then at ambient temperatures for 18hours. Triethylamine hydrochloride is removed by filtration and thefiltrate is taken to dryness. The residual oil is distilled to give 2.6g. of product, b.p. 156°-157° C. (0.07 mm.).

EXAMPLE 958A Preparation of4-(dimethylisopropylsiloxy)-2-(6-carbodimethylisopropylsiloxyhexyl)cyclopent-2-en-1-one

Treatment of 1 g. of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-onein 2 ml. of dry N,N-dimethylformamide containing 1.81 g. ofdimethylisopropylsilyl chloride [E. J. Crey, R. K. Verma, J. Amer. Chem.Soc., 93, 7320 (1971)] 1.57 g. of triethylamine in 2 ml. ofN,N-dimethylformamide in the manner described in Example 958 gives 1.45g. of product after two evaporations with toluene.

EXAMPLE 959 Preparation of4-(dimethyl-t-butylsiloxy)-2-(6-carbodimethyl-t-butylsiloxyhexyl)cyclopent-2-en-1-one

To a 0° C. solution of 2.0 gm. (8.55 mole)4-hydroxy-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 94) and 3.65gm. (54 mole) of imidazole in 5 ml. of dimethylformamide is added aslurry consisting of 4.07 gm. (27 mole) of dimethyl-t-butyl chlorosilanein 5 ml. of dimethylformamide. The slurry is rinsed in with anadditional 1 ml. of dimethylformamide. The ice-bath is removed and thesolution is stirred at 37° C. for four hours. The solution is thenpoured into 140 ml. of water and the aqueous solution is extracted twicewith 70 ml. of isomeric hexanes. The organic layers are combined, driedwith magnesium sulfate and concentrated in vacuo to an oil. Toluene (50ml.) is added twice and evaporated in vacuo to remove unwanted lowboiling impurities.

The residue is maintained under active vacuum overnight to give 3.38 gm.(7.45 mole) of an oil, that shows no hydroxyl or carboxyl absorption inthe infrared. τ max: 1720 cm⁻¹ (unsaturated ketone and silyl ester).840, 815, 795, 780 cm⁻¹ (silyl ether and silyl ester).

EXAMPLE 960 Preparation of dl-prostaglandin E₁ and dl-epi-prostaglandinE₁

To a solution of 4.790 g. (0.0091 mole) of3-(p-anisyldiphenylmethoxy)-trans-1-iodo-1-octene (Example 956) in 5 ml.of toluene cooled to -78° C. under an inert atmosphere is added 3.9 ml.of 2.34 M n-butyllithium in hexane. The resulting solution is warmed to-40° C. and is maintained at this temperature for 1 hour. To thesolution containing 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithiumis then added 3.6 ml. of a 2.44 M solution of trimethylaluminum inheptane and the mixture is allowed to warm to 0° C. The solutioncontaining lithiumtrimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate is thenadded to a solution of 3.30 g. (0.00726 mole) of2-(6-carbo-t-butyldimethylsiloxyhexyl)-4-(t-butyldimethylsiloxy)-2-cyclopentenone(Example 959) dissolved in 10 ml. of ether cooled to -45° C. under aninert atmosphere. The resulting solution is allowed to warm to roomtemperature and is stirred at ambient temperatures for 17 hours. Thesolution is then poured onto a mixture of 5 ml. of concentratedhydrochloric acid and 150 g. of ice. This mixture is stirred until theice melts and is extracted into ether. The organic phase is washed withice cold water and cold saturated brine, dried (Na₂ SO₄), and isevaporated (<37° C.) in vacuo. The resulting oil is then heated to 38°C. for 23 hours under an inert atmosphere with 100 ml. of 3:1:1 (V:V:V)acetic acid-tetrahydrofuran-water. The mixture is then evaporated with150 ml. of xylene in vacuo (<38° C.) to yield an oil. Chromatography ofthis oil upon 115 g. of Silic AR CC-4 (Mallinckrodt) using abenzene-ethyl acetate gradient as eluent yields dl-prostaglandin E₁,m.p. 108-112 (from ethyl acetate) and dl-15-epi-prostaglandin E₁.

EXAMPLE 961 Preparation of 3-triphenylmethoxy-trans-1-octenyllithium

To a solution of 4.96 g. of 1-iodo-3-triphenylmethoxy-trans-1-octane(Example 730) in 10 ml. of toluene cooled to -78° C. is added under aninert atmosphere 1 molar equivalent of n-butyllithium dissolved inhexane. The reaction mixture is allowed to warm to -40° C. and is thenmaintained at that temperature for 1 hour to yield a hydrocarbonsolution of 3-triphenylmethoxy-trans-1-octenyllithium.

EXAMPLE 962 Preparation of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium

To a solution of 5.26 g. of1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene (Example 958) in 10ml. of toluene, cooled to -78° C., is added under an inert atmosphere 1molar equivalent of n-butyllithium dissolved in hexane. The reactionmixture is allowed to warm to -40° C. and is maintained at thattemperature for 1 hour to yield a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium

EXAMPLE 963 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-trimethylalanate

to a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40° C. is added under an inert atmosphere 1molar equivalent of trimethylaluminum dissolved in heptane to yield ahydrocarbon solution of the title compound.

EXAMPLE 964 Preparation of lithium[3-p-anisyldiphenylmethoxy)-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of3-(p-anisyldiphenyl-methoxy)-trans-1-octenyllithium (Example 962) cooledto -40° C. is added under an inert atmosphere 1 molar equivalent oftrimethylaluminum dissolved in hexane to yield a hydrocarbon solution ofthe title compound.

EXAMPLE 965 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-tri-n-propylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40° C. is added under an inert atmosphere 1molar equivalent of tri-n-propylaluminum dissolved in hexane to yield ahydrocarbon solution of the title compound.

EXAMPLE 966 Preparation of lithium[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-tri-n-hexylalanate

To a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) cooledto -40° C. is added under an inert atmosphere 1 molar equivalent totri-n-hexylaluminum dissolved in heptane to yield a hydrocarbon solutionof the title compound.

EXAMPLE 967 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-tri-n-decylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40° C. is added under an inert atmosphere 1molar equivalent of tri-n-decylaluminum dissolved in heptane to yield ahydrocarbon solution of the title compound.

EXAMPLE 968 Preparation of lithiumdi-(3-triphenylmethoxy-trans-1-octenyl)-dimethylalanate

To a hydrocarbon solution of dimethylaluminum chloride cooled to -78° C.is added under an inert atmosphere 2 molar equivalents of3-triphenylmethoxy-trans-1octenyllithium (Example 961) dissolved intoluene-hexane solvent. The mixture is allowed to warm to 0° C. to yielda hydrocarbon solution of the title compound.

EXAMPLE 969 Preparation of lithiumdi-[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-diethylalanate

To a hexane solution of diethylaluminum chloride cooled to -78° C. isadded under an inert atmosphere 2 molar equivalents of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962)dissolved in toluene-hexane solvent. The mixture is allowed to warm to0° c. to yield a hydrocarbon solution of the title compound.

EXAMPLE 970 Preparation of lithiumtri-(3-triphenylmethoxy-trans-1-octenyl)-ethylalanate

To a hydrocarbon solution of ethylaluminum dichloride cooled to -78° C.is added under an inert atmosphere 3 molar equivalents of3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved intoluene-hexane solvent. The mixture is allowed to warm to 0° C. to yielda hydrocarbon solution of the title compound.

EXAMPLE 971 Preparation of lithiumtetra-(3-triphenylmethoxy-trans-1-octenyl)alanate

To a well stirred mixture of anhydrous aluminum chloride and hexanecooled to -78° C. is added under an inert atmosphere 4 molar equivalentsof 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved intoluene-hexane. The mixture is allowed to warm to 0° C. to yield thetitle compound.

EXAMPLE 972 Preparation of lithiumtetra-(3-p-anisyldiphenylmethoxy-trans-1-octenyl)alanate

To a well stirred mixture of anhydrous aluminum chloride and hexanecooled to -78° C. is added under an inert atmosphere 4 molar equivalentsof 3-p-anisyldiphenylmethoxy-trans-1-octenyllithium (Example 962)dissolved in toluene-hexane. The mixture is allowed to warm to 0° C. toyield the title compound.

EXAMPLES 973-981

Substitution of lithiumtrimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate in Example 957 withthe lithium alanates of Examples 964, 965, 966, 967, 968, 969, 970, 971or 972 is productive of the methyl esters of d,1-11-deoxy-prostaglandinE₁ and d,11-deoxy-15-epi-prostaglandin E₁.

EXAMPLES 982-990

Substitution of lithium trimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate of Example 960 withthe lithium alanates of Examples 965, 966, 967, 968, 969, 970, 971 or972 is productive of d,l-prostaglandin-E₁ and d,l-15-epi-prostaglandinE₁.

EXAMPLE 991 Preparation of hexanoyl bromide

A mixture of 300 g. of hexanoic acid and 260 g. of phosphorus tribromideis heated at 80° C. for 1.5 hours with stirring and protection frommoisture. The mixture is cooled and the upper phase is decanted into adistilling flask. Distillation of this material yields 400 g. of thecolorless acid bromide, b.p. 51-53° C. (10 torr.).

EXAMPLE 992 Preparation of 1-bromo-trans-1-octen-3-one

A mixture of 300 g. of aluminum bromide and 250 ml. of1,2-dibromoethane, cooled in an ice bath and protected from moisture, issaturated with acetylene. To the mixture is added with ice cooling 150g. of hexanoyl bromide (Example 991) over a period of 20 minutes and theresulting mixture is treated with acetylene until gas uptake ceases. Thereaction mixture is poured onto 500 ml. of saturated brine and 500 g. ofice. The resulting mixture is extracted twice with 500 ml. of ether. Thecombined organic extracts are washed twice with 500 ml. of saturatedbrine and dried with anhydrous sodium sulfate. To the organic phase isadded 5 g. of hydroquinone and the solvent is evaporated in vacuo toyield the crude 1-bromo-trans-1-octen-3-one.

EXAMPLE 993 Preparation of 1-bromo-trans-1-octen-3-o1

To an ice cooled mixture of 20 g. of sodium borohydride in 800 ml. ofanhydrous ethanol is added 160 g. of crude 1-bromo-trans-1-octen-3-one(Example 992) over a period of 0.5 hour. The mixture is stirred for 2hours with ice cooling and is then partitioned between ice water andbenzene. The organic phase is washed with water and saturated brine,dried (Na₂ SO₄), and evaporated to an oil. Distillation gives theproduct as an oil, b.p. 66°-68° C. (0.025 torr.).

EXAMPLE 994 Preparation of 4,4-dimethyl-1-octyn-3-o1

To a solution of 20.2 g. (0.220 mole) of lithiumacetylide-ethylenediamine complex in 100 ml. of dry dimethylsulfoxide isadded 25.6 g. (0.200 mole) of 2,2-dimethyl-1-hexanal, prepared accordingto the procedure of G. Stork and S. R. Dowd, J. Amer. Chem. Soc., 85,2178 (1963), in 25 ml. of dimethylsulfoxide at a rate to maintain atemperature of 25° C. (cooling). The mixture is then maintained at 25°C. for 2 hours and is poured onto ice and excess hydrochloric acid. Themixture is extracted with ether and the organic phase is washed withwater and saturated brine, dried (Na₂ SO₄), and evaporated to an oil.Distillation in vacuo yields the product as a colorless oil.

EXAMPLE 995 Preparation of 4,4- dimethyl-3-tetrahydropyranyloxy-1-octyne

To a solution of 23.1 g. (0.150 mole) of 4,4-dimethyl-1-octyn-3-o1(Example 994) in 126 g. of freshly distilled dihydropyran is added 1drop of phosphorus oxychloride and the solution is maintained at ambienttemperature in a tightly stoppered flask for 20 hours. Five drops oftriethylamine are then added and the mixture is evaporated in vacuo toan oil. The oil is chromatographed on 600 g. of silica gel and theproduct is eluted with 5% ethyl acetate in benzene yielding a colorlessoil.

EXAMPLE 996 Preparation of 4,4-dimethyl-1-iodo-trans-1-octen-3-o1

To 233 ml. of a 0.43% solution of disiamylborane in diglyne cooled to 0°C. under an inert atmosphere is added 23.8 g. (0.100 mole)4,4-dimethyl-3-tetrahydropyramyloxy-1-octyne (Example 995). The mixtureis allowed to come to room temperature and is stirred at ambienttemperature for 3 hours. The solution is cooled to 0° C. and 22.5 g.(0.30 mole) of triethylamine oxide is added portionwise such that thetemperature is maintained at 0°-5° C. The mixture is stirred at 0° C.for 1 hour and is then poured into 150 ml. of 1 N sodium hydroxidefollowed immediately by a solution of 25.4 g. (0.100 mole) of iodine in60 ml. of tetrahydrofuran. The mixture is stirred at ambienttemperatures for 0.5 hour and poured into 500 ml. of water. The mixtureis decolorized by addition of sodium thiosulfate solution and isextracted into ether. The organic phase is washed with water and thesolvent is removed in vacuo. The residue is stirred at room temperaturefor 20 hours with 900 ml. 3:1:1 tetrahydrofuran-acetate acid-water. Thesolution is evaporated in vacuo and the residue is chromatographed onsilica gel in benzene using 10-20% ethylacetate in benzene.

EXAMPLE 997 Preparation of4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 11.2 g. (0.0396 mole) of4,4-dimethyl-1-iodo-trans-1-octen-3-ol (Example 996) with 12.8 g. oftriphenylmethyl bromide in 50 ml. of pyridine and purification onFlorisil®, all as described in Example 728 gives the title compound.

EXAMPLE 998 Preparation of 5,5-dimethyl-1-octyn-3-ol

Treatment of 20.2 g. (0.220 mole) of lithium acetylide-ethylenediamecomplex in 100 ml. of dimethylsulfoxide with 25.6 g. (0.200 mole) of3,3-dimethylhexanal [prepared according to the procedure of A. W.Burgstahler, J. Amer. Chem. Soc., 82, 4681 (1960)] and distillation ofthe product, all as described in Example 994 yields the title compound.

EXAMPLE 999 Preparation of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne

Treatment of 23.1 g. (0.150 mole) of 5,5-dimethyl-1-octyn-3-ol (Example998) with 126 g. of dihydropyran and 1 drop of phosphorus oxychloride asdescribed in Example 995 gives the title compound.

EXAMPLE 1000 Preparation of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol

Treatment of 23.8 g. (0.100 mole) of5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) successivelywith 233 ml. of 0.43 M disiamylborane in diglyme, 22.5 g. oftrimethylamine oxide, 150 ml. of 1 N sodium hydroxide, 25.4 g. ofiodine, and 900 ml. of 3:1:1 tetrahydrofuran-acetic acid-water asdescribed in Example 996 gives the title compound.

EXAMPLE 1001 Preparation of5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 6.0 g. of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol (Example1000) with 6.9 g. of triphenylmethyl bromide in 30 ml. of pyridine andpurification on Florisil®, all as described in Example 728 gives thetitle compound.

EXAMPLE 1002 Preparation of4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene(Example 997) with n-butyllithium in the manner of Example 961 providesa toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1003 Preparation of5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene(Example 1001) with n-butyllithium in the manner of Example 961 providesa toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1004 Preparation of lithium(4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to themethod of Example 963 from a hydrocarbon solution of4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium (Example 1002)and trimethylaluminum.

EXAMPLE 1005 Preparation of lithium(5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

A hydrocarbon solution of the subject alanate is prepared from ahydrocarbon solution of 5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium (Example 1003) and trimethylaluminum according to the procedureof Example 963.

EXAMPLES 1006-1031

Treatment of the cycloalkanones of Table 16 which follows with theindicated alanates according to the procedure of Example 957 providesthe product 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoates ofthe table. The intermediate corresponding 15-O-triphenylmethylderivatives are obtained prior to treatment with aqueous acetic acid.

                  TABLE 16                                                        ______________________________________                                                          Product from reaction with                                                    lithium (4,4-Dimethyl-3-                                          Starting cyclo-                                                                           triphenylmethoxy-trans-1-                                   Ex-   alkenone of octenyl)trimethylalanate                                    ample Example     (Example 1004)                                              ______________________________________                                        1006  13          ethyl 9-oxo-15-hydroxy-16-                                                    16-dimethyl-13-trans-pro-                                                     atenoate                                                    1007  23          ethyl 9-oxo-15-hydroxy-16-                                                    16-dimethyl-7a,7b-bishomo-                                                    13-trans-prostenoate                                        1008  31          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-ethyl-13-                                                       trans-prostenoate                                           1009  41          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3,3-dimethyl-                                                     13-trans-prostenoate                                        1010  46          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3-oxa-13-trans-                                                   prostenoate                                                 1011  53          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-7-nor-13-trans-                                                   prostenoate                                                 1012  70          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-fluoro-13-                                                      trans-prostenoate                                           1013  84          n-decyl 9-oxo-15-hydroxy-                                                     16,16-dimethyl-13-trans-                                                      prostenoate                                                 1014  99          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-methyl-13-                                                      trans-prostenoate                                           1015  111         ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-10a-homo-13-                                                      trans-prostenoate                                           1016  118         ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3-thia-13-trans-                                                  prostenoate                                                 1017  900         methyl 9-oxo-15-hydroxy-16,-                                                  16-dimethyl-5-cis,13-trans-                                                   prostadienoate                                              1018  79          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-phenyl-13-                                                      trans-prostenoate                                           1019  13          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-13-trans-pro-                                                     stenoate                                                    1020  23          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-7a,7b-bishomo-                                                    13-trans-prostenoate                                        1021  31          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-ethyl-13-                                                       trans-prostenoate                                           1022  41          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3,3-dimethyl-                                                     13-trans-prostenoate                                        1023  46          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3-oxa-13-trans-                                                   prostenoate                                                 1024  53          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-7-nor-13-trans-                                                   prostenoate                                                 1025  70          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-fluoro-13-                                                      trans-prostenoate                                           1026  84          n-decyl 9-oxo-15-hydroxy-                                                     17,17-dimethyl-13-trans-                                                      prostenoate                                                 1027  99          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-methyl-13-                                                      trans-prostenoate                                           1028  111         ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-10a-homo-13-                                                      trans-prostenoate                                           1029  118         ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3-thia-13-trans-                                                  prostenoate                                                 1030  900         methyl 9-oxo-15-hydroxy-                                                      17,17-dimethyl-5-cis,13-                                                      trans-prostadienoate                                        1031  79          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-phenyl-13-                                                      trans-prostenoate                                           ______________________________________                                    

EXAMPLES 1032-1055

Saponification of the 16,16-dimethyl or 17,17-dimethyl13-trans-prostenoate alkyl esters of Table 17 below by the method ofExample 122 provides the corresponding prostenoic acids of the Table.

                  TABLE 17                                                        ______________________________________                                                          Product 16,16-dimethyl or                                         Starting alkyl                                                                            17,17-dimethyl-9-oxo-15-                                    Ex-   ester of    hydroxy-13-trans-proste-                                    ample Example     noic acid                                                   ______________________________________                                        1032  1006        9-oxo-15-hydroxy-16,16-di-                                                    methyl-13-trans-prostenoic                                                    acid                                                        1033  1007        9-oxo-15-hydroxy-16,16-di-                                                    methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                       1034  1008        9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-ethyl-13-trans-                                                      prostenoic acid                                             1035  1009        9-oxo-15-hydroxy-16,16-di-                                                    methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                       1036  1010        9-oxo-15-hydroxy-16,16-di-                                                    methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                                1037  1011        9-oxo-15-hydroxy-16,16-di-                                                    methyl-7-nor-13-trans-pro-                                                    stenoic acid                                                1038  1032        9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-fluoro-13-trans-                                                     prostenoic acid                                             1039  1014        9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-methyl-13-trans-                                                     prostenoic acid                                             1040  1015        9-oxo-15-hydroxy-16,16-di-                                                    methyl-10a-homo-13-trans-                                                     prostenoic acid                                             1041  1016        9-oxo-15-hydroxy-16,16-di-                                                    methyl-3-thia-13-trans-                                                       prostenoic acid                                             1042  1017        9-oxo-15-hydroxy-16,16-di-                                                    methyl-5-cis,13-trans-pro-                                                    stadienoic acid                                             1043  1018        9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-phenyl-13-trans-                                                     prostenoic acid                                             1044  1019        9-oxo-15-hydroxy-17,17-di-                                                    methyl-13-trans-prostenoic                                                    acid                                                        1045  1020        9-oxo-15-hydroxy-17,17-di-                                                    methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                       1046  1021        9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-ethyl-13-trans-                                                      prostenoic acid                                             1047  1022        9-oxo-15-hydroxy-17,17-di-                                                    methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                       1048  1023        9-oxo-15-hydroxy-17,17-di-                                                    methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                                1049  1024        9-oxo-15-hydroxy-17,17-di-                                                    methyl-7-nor-13-trans-pro-                                                    stenoic acid                                                1050  1025        9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-fluoro-13-trans-                                                     prostenoic acid                                             1051  1027        9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-methyl-13-trans-                                                     prostenoic acid                                             1052  1028        9-oxo-15-hydroxy-17,17-di-                                                    methyl-10a-homo-13-trans-                                                     prostenoic acid                                             1053  1029        9-oxo-15-hydroxy-17,17-di-                                                    methyl-3-thia-13-trans-pro-                                                   stenoic acid                                                1054  1030        9-oxo-15-hydroxy-17,17-di-                                                    methyl-5-cis,13-trans-pro-                                                    stadienoic acid                                             1055  1031        9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-phenyl-13-trans-                                                     prostenoic acid                                             ______________________________________                                    

EXAMPLES 1056-1081

Treatment of the 9-oxo- acids and esters of Table 18 below with lithiumperhydro-9β-boraphenalyl halides by the procedure of Example 737provides the 9α,15-dihydroxy-16,16-dimethyl or17,17-dimethyl-13-trans-prostenoic acid of the Table.

                  TABLE 18                                                        ______________________________________                                                          Product 9α-15-Dihydroxy-16,-                                Starting 9-oxo                                                                            16-dimethyl or 17,17-di-                                    Ex-   derivative of                                                                             methyl-13-trans-prostenoic                                  ample Example     acids or esters                                             ______________________________________                                        1056  1032        9α,15-dihydroxy-16,16-di-                                               methyl-13-trans-prostenoic                                                    acid                                                        1057  1033        9α,15-dihydroxy-16,16-di-                                               methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                       1058  1034        9α,15-dihydroxy-16,16-di-                                               methyl-2-ethyl-13-trans-                                                      prostenoic acid                                             1059  1035        9α,15-dihydroxy-16,16-di-                                               methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                       1060  1036        9α,15-dihydroxy-16,16-di-                                               methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                                1061  1037        9α,15-dihydroxy-16,16-di-                                               methyl-7-nor-13-trans-pro-                                                    stenoic acid                                                1062  1038        9α,15-dihydroxy-16,16-di-                                               methyl-2-fluoro-13-trans-                                                     prostenoic acid                                             1063  1013        n-decyl 9α,15-dihydroxy-16,-                                            16-dimethyl-13-trans-proste-                                                  noate                                                       1064  1039        9α,15-dihydroxy-16,16-di-                                               methyl-2-methyl-13-trans-                                                     prostenoic acid                                             1065  1040        9α,15-dihydroxy-16,16-di-                                               methyl-10a-homo-13-trans-                                                     prostenoic acid                                             1066  1041        9α,15-dihydroxy-16,16-di-                                               methyl-3-thia-13-trans-pro-                                                   stenoic acid                                                1067  1042        9α,15-dihydroxy-16,16-di-                                               methyl-5-cis,13-trans-                                                        prostadienoic acid                                          1068  1043        9α,15-dihydroxy-16,16-di-                                               methyl-2-phenyl-13-trans-                                                     prostenoic acid                                             1069  1044        9α,15-dihydroxy-17,17-di-                                               methyl-13-trans-prostenoic                                                    acid                                                        1070  1045        9α,15-dihydroxy-17,17-di-                                               methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                       1071  1046        9α,15-dihydroxy-17,17-di-                                               methyl-2-ethyl-13-trans-                                                      prostenoic acid                                             1072  1047        9α,15-dihydroxy-17,17-di-                                               methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                       1073  1048        9α,15-dihydroxy-17,17-di-                                               methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                                1074  1049        9α,15-dihydroxy-17,17-di-                                               methyl-7-nor-13-trans-pro-                                                    stenoic acid                                                1075  1050        9α,15-dihydroxy-17,17-di-                                               methyl-2-fluoro-13-trans-                                                     prostenoic acid                                             1076  1026        n-decyl 9α,15-dihydroxy-                                                17,17-dimethyl-13-trans-                                                      prostenoate                                                 1077  1051        9α,15-dihydroxy-17,17-di-                                               methyl-2-methyl-13-trans-                                                     prostenoic acid                                             1078  1052        9α,15-dihydroxy-17,17-di-                                               methyl-10a-homo-13-trans-                                                     prostenoic acid                                             1079  1053        9α,15-dihydroxy-17,17-di-                                               methyl-3-thia-13-trans-                                                       prostenoic acid                                             1080  1054        9α,15-dihydroxy-17,17-di-                                               methyl 5-cis,13-trans-pro-                                                    stadienoic acid                                             1081  1055        9α,15-dihydroxy-17,17-di-                                               methyl-2-phenyl-13-trans-                                                     prostenoic acid                                             ______________________________________                                    

EXAMPLE 1082

A solution of methyl9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostatrienoate (Example 374) intetrahydrofuran is added to 1.1 equivalent of lithiumperhydro-9β-boraphenyalyl hydride in tetrahydrofuran at -78° C. After 30minutes equal volumes of 5% aqueous sodium carbonate and 30% aqueoushydrogen peroxide is added, and the solution is stirred 15 minutes. Thesolution is diluted with water and extracted with ether. The organicphase is dried (magnesium sulfate) and concentrated in vacuo to givemethyl 9α,15α-dihydroxy-5-cis,13-trans,17-cis-prostatrienoate,contaminated with methyl9β,15α-dihydroxy-5cis,13trans,17cis-prostatienoate. The crude mixture ofesters is dissolved in methylene chloride and added to a refluxingsolution of 1.2 equivalents of 2,3-dichloro-5,6-dicyanobenzoquinone(DDQ) in methylene chloride. After 5 hours, the solution is cooled andfiltered. The filtrate is diluted with two volumes of ether, extractedwith 5% aqueous sodium carbonate and dried with magnesium sulfate. Thesolution is concentrated in vacuo to give methyl9α-hydroxy-15-oxo-5cis-13-trans, 17cis-prostatrienoate and9β-hydroxy-15-oxo-5cis, 13trans,17cis-prostatrienoate. The crudematerial is dissolved in benzene and 1.2 equivalents each oftriethylamine and trimethylsilyl chloride is added. The triethylaminehydrochloride is removed by filtration and the solution is concentratedin vacuo to give methyl9α-trimethylsiloxy-15-keto-5cis,13trans,17cis-prostatrienoate and thecorresponding 9β-trimethylsiloxy derivative.

The siloxy derivatives are dissolved in ether at 0° C. and 1.05equivalents of methyl magnesium bromide in ether is added. After thereaction is complete, the solution is poured into saturated aqueousammonium chloride and extracted with ether. The ether is dried andconcentrated in vacuo to give methyl9α-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate,and methyl9α-trimethylsiloxy-15β-hydroxy-15α-methyl-5cis,13trans,17-cis-prostatrienoate,methyl9β-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate,and methyl 9β-trimethylsiloxy-15β-hydroxy-15α-methyl5cis,13trans,17cis-prostatrienoate. Hydrolysis of the siloxy functionsof each in a solution of methanol, water and acetic acid (approximately10:1:1, 3 hours ambient temperatures) and gives methyl9α,15α-dihydroxy-15β-methyl-5cis-13trans,17cis-prostatrienoate, methyl9α,15β-dihydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoate, methyl9β,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate andmethyl 9β,15β-dihydroxy-15α-methyl-5-cis,13-trans,17cis-prostatrienoateseparated by dry column chromatography and further purified by partitionchromatography saponification (method of Example 122) of each componentin 50% aqueous methanol with potassium hydroxide gives the correspondingfree acids.

Treatment of a solution of methyl 9α,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate in methylene chloride with Collins reagent(CrO₃ -pyridine in methylene chloride) give methyl9-oxo-15α-hydroxy-15β-methyl-5cis,13-trans,17cis-prostatrienoate,saponification of which (method of Example 122) gives9-oxo-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate acid.

Similar treatment of the 15β-hydroxy esters gives methyl9-oxo-15β-hydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoate whichgives 9-oxo-15β-hydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoicacid after saponification.

EXAMPLES 1083-1101

Treatment of the 9-oxo-15-hydroxy prostenoic esters of Table 18A belowby the sequence of reactions described in Example 1082 is productive ofthe 9α,15-dihydroxy-15-methyl and the 9-oxo-15-hydroxy-15-methylproducts of the table. Also prepared in the course of these reactionsequences are the ethyl (methyl for Example 1101) esters correspondingto the products of the table, the 9β-hydroxy derivatives correponding tothe listed 9α-hydroxy derivatives and their ethyl esters, the 15-ketoderivatives of the 9α- and 9β-hydroxy compounds corresponding to the9-oxo starting compounds, and the 9α- or 9β-trimethyl-silyloxy ethylesters of the 15-keto and 15-hydroxy-15-methyl compounds. In all casesboth the 15α-hydroxy-15β-methyl and the 15β-hydroxy-15α-methyl produtsand intermediates are obtained. These epimers are separable bychromatographic procedures.

                  TABLe 18A                                                       ______________________________________                                              Starting 9-oxo-                                                         Ex-   15-hydroxy-ester                                                                           Product 15-hydroxy-                                        ample of Example   15-methyl derivative                                       ______________________________________                                        1083  260          9-oxo-15-methyl-15-                                                           hydroxy-2-ethyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-ethyl-13-                                                         trans-prostenoic acid                                      1084  261          9-oxo-15-hydroxy-15-                                                          methyl-3,3-dimethyl-                                                          13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-                                                            3,3-dimethyl-13-trans-                                                        prostenoic acid                                            1085  262          9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-13-trans-                                                        prostenoic acid and                                                           9α,15-dihydroxy-15-                                                     methyl-3-oxa-13-trans-                                                        prostenoic acid                                            1086  264          9-oxo-15-hydroxy-15-                                                          methyl-2-fluoro-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-fluoro-                                                           13-trans-prostenoic                                                           acid                                                       1087  266          9-oxo-15-hydroxy-15-                                                          methyl-2-phenyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-phenyl-                                                           13-trans-prostenoic                                                           acid                                                       1088  267          9-oxo-15-hydroxy-15-                                                          methyl-2-methyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-methyl-                                                           13-trans-prostenoic                                                           acid                                                       1089  268          9-oxo-15-hydroxy-15-                                                          methyl-10a-homo-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-10a-homo-                                                           13-trans-prostenoic                                                           acid                                                       1090  272          9-oxo-15-hydroxy-15-                                                          methyl-3-thia-13-                                                             trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-3-thia-13-                                                          trans-prostenoic acid                                      1091  362          9-oxo-15-hydroxy-15-                                                          methyl-3-thia-20-                                                             methyl-13-trans-pro-                                                          stenoic acid and 9α,15-                                                 dihydroxy-15-methyl-3-                                                        thia-20-methyl-13-                                                            trans-prostenoic acid                                      1092  343          9-oxo-15-hydroxy-15-                                                          methyl-2,20-dimethyl-                                                         13-trans-prostenoic                                                           acid and 9α,15-di-                                                      acid and 9α,15-di-                                                      hydroxy-15-methyl-                                                            2,20-dimethyl-13-                                                             trans, prostenoic acid                                     1093  323          9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-20-methyl-                                                       13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-3-                                                          oxa-20-methyl-13-                                                             trans-prostenoic acid                                      1094  284          9-oxo-15-hydroxy-15-                                                          methyl-13-trans, 17-                                                          cis-prostadienoic acid                                                        and 9α,15-dihydroxy-15-                                                 methyl-13-trans,17-                                                           cis-prostadienoic acid                                     1095  287          9-oxo-15-hydroxy-15-                                                          methyl-7a,7b-bishomo-                                                         13-trans,17-cis-pro-                                                          stadenoic acid and 9a,                                                        15-dihydroxy-15-methyl-                                                       7a,7b-bishomo-13-                                                             trans, 17-cis-prosta-                                                         dienoic acid                                               1096  290          9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-13-trans,                                                        17-cis-prostadienoic                                                          acid and 9a,15-dihydro-                                                       xy-15-methyl-3-oxa-13-                                                        trans, 17-cis-prosta-                                                         dienoic acid                                               1097  291          9-oxo-15-hydroxy-15-                                                          methyl-7-nor-13-trans,                                                        17-cis-prostadienoic                                                          acid and 9α ,15-di-                                                     hydroxy-15-methyl-7-                                                          nor-13-trans, 17-cis-                                                         prostadienoic acid                                         1098  292          9-oxo-15-hydroxy-15-                                                          methyl-2-fluoro-13-                                                           trans, 17-cis-prosta-                                                         dienoic acid and 9α,                                                    15-dihydroxy-15-methyl-                                                       2-fluoro-13-trans,                                                            17-cis-prostadienoic                                                          acid                                                       1099  293          9-oxo-15-hydroxy-15-                                                          methyl-7a -homo-13-                                                           trans, 17-cis-prosta-                                                         dienoic acid and 9α, 15-                                                dihydroxy-15-methyl-7a-                                                       homo-13-trans, 17-cis-                                                        prostadienoic acid                                         1100  300          9-oxo-15-hydroxy-15-                                                          methyl-3-thia-13-trans,                                                       17-cis-prostadienoic                                                          acid and 9α,15-di-                                                      hydroxy-15-methyl-3-                                                          thia-13-trans, 17-cis-                                                        prostadienoic acid                                         1101  733          9-oxo-15-hydroxy-15-                                                          methyl-13-cis, 17-cis-                                                        prostadienoic acid and                                                        9α,15-dihydroxy-15-                                                     methyl-13-cis, 17-cis                                                         prostadienoic acid                                               *methyl 15-hy-                                                                droxy-9-oxo-                                                                  13-cis-prost-                                                                 enoate only                                                             ______________________________________                                    

EXAMPLES 1102-1104

Hydrogenation of the 13-trans-prostenoic acids listed in Table 19 belowby the procedure described in Example 699 is productive of the productpostenoic acids of the table. The product epimers are separable bychromatographic procedures.

                  TABLE 19                                                        ______________________________________                                              Starting 15-hy-                                                               droxy-15-methyl-                                                                             Product 15-hydroxy-                                      Ex-   13-trans-pros- 15-methyl-prostanoic                                     ample tenoic acid    acid                                                     ______________________________________                                        1102  9-oxo-15-hydroxy-                                                                            9-oxo-15-hydroxy-15-                                           15-methyl-3-oxa-                                                                             methyl-3-oxa-prostanoic                                        13-trans-pros- acid                                                           tenoic acid                                                                   (Example 1085)                                                          1103  9α,15-dihydroxy-                                                                       9α,15-dihydroxy-15-                                      15-methyl-3-oxa-                                                                             methyl-3-oxa-pros-                                             13-trans-pros- tanoic acid                                                    tenoic acid                                                                   (Example 1085)                                                          1104  9-oxo-15-hydroxy-                                                                            9-oxo-15-hydroxy-15-                                           15-methyl-10a- methyl-10a-homo-pros-                                          homo- 13-trans-                                                                              tanoic acid                                                    prostenoic acid                                                               (Example 1089)                                                          ______________________________________                                    

EXAMPLE 1105 Preparation of allcis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxide-cyclopentanol

A solution of 1.42 g. (10.0 moles) ofall-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-lactol (E. J. Coreyand R. Noyori, Tetrahedron Letters, 1970, 311) in 5 ml. of DMSO is addedto a stirred solution with the Whttig reagent [E. J.Corey et al, JACS,91 5675 (1969) also Example 1108 prepared from 13.3 g. (30 moles) of4-carboxybutyltriphenylphosphonium bromide 2.52 g. (60 moles) of 57%sodium hydride dispersion, and 70 ml. of DMSO at 16° C. during 1 minute.

The solution is stirred at ambient temperatue for 20 hours and pouredinto a stirred mixture of methylene chloride, ice, and hydrochloricacid. The organic phase is separated, and the aqueous phase is extractedwith methylene chloride, saturated with sodium chloride, and extractedwith ether. The combined organic extracts are partitioned with sodiumbicarbonate. The aqueous basic extract is acidified with dilute HCl,saturated with sodium chloride, and extracted with ethyl acetate. Theextract is washed with brine, dried over magnesium sulfate, andconcentrated to give the crude title compound as an orange oil.

EXAMPLE 1106 Preparation ofall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxide-cyclopentanone

To a stirred solution of ca. 1.6 moles of crudeall-cis-2-(6-carboxy-2-cis-hexanyl)-3,4-oxidocyclopentanol (Example1105) in 1.6 ml. of ether is added 1.6 ml. of 4.0 N chromic acid in 4 Nsulfuric acid at 0° C. during 9 minutes. After stirring for 5 minutes at0° C. the solution is diluted with brine, ether, and ethyl acetate. Theorganic phase is treated with isopropanol, washed with brine and driedover magnesium sulfate. Evaporation of the solvent gives the subjectcompound as an oil.

EXAMPLE 1107 Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycylopent-2-en-1-one

A solution of 1.0 mmole ofall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example1106) and 3.0 mmoles of sodium carbonate in 15 ml. of water is allowedto stand at room temperature for 3 hours. The solution is acidified withHCl, saturated with sodium chloride, and extracted with ether. Theextract is washed with brine, dried over magnesium sulfate, andconcentrated to give a mixture of the title compound and the isomericcompound, 2-(6-carboxy-2-cis-hexenyl)-3-hydroxycyclopent-4-en-1-one.Further treatment of this mixture with N/10 sodium hydroxide at roomtemperature for 30 minutes causes the rearrangment of the latter isomerto the title compound, which is isolated from basic solution as above.

EXAMPLE 1107a Preparation of2-(6carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

Treatment ofcis-anti-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-ν-lactol (R. J.Corey and R. Noyori Tetrahedron Letters, 1970, 311) with4-carboxytriphenylphosphonium bromide as described in Example 1105 isproductive of2β-(6-carboxy-2-cis-hexenyl)-3α,4α-oxidocyclopentan-1.beta.-ol which onoxidation by the method of Example 1106 provides2β-(6-carboxy-2-cis-hexenyl)-3α,4α-oxidocyclopentanone, which in time ontreatment with aqueous base by the procedure of Example 1107 furnishesthe subject compound.

EXAMPLE 1108 Preparation of 4-carboxybutyltriphenylphosphonium bromide

A mixture of 103 g. of 5-bromovalevic acid and 152 g. oftriphenylphosphine in 400 ml. of acetonitrile is refluxed for 48 hours,cooled, diluted with 100 ml. of benzene and allowed to crystallize. Thecrystals are filtered, washed with benzene and ether, to yield colorlessmaterial, m.p. 207°-209° C.

EXAMPLES 1109-1111

Treatment of the indicated ω-bromoalkanoic acids of Table 20 below withtriphenylphosphine by the method described in Example 1108 produces thephosphonium bromide of the table.

                  TABLE 20                                                        ______________________________________                                        Ex-   Starting ω-bromo-                                                                      Product                                                  ample alkanone acid  Phosphonium bromide                                      ______________________________________                                        1109  4-bromo-n-butyric                                                                            3-carboxypropyltri-                                            acid           phenylphosphonium                                                             bromide                                                  1110  6-bromo-n-hexanoic                                                                           5-carboxypentyltri-                                            acid           phenylphosphonium                                                             bromide                                                  1111  7-bromo-n-hepta-                                                                             6-carboxyhexyltri-                                             noic acid      phenylphosphonium                                                             bromide                                                  ______________________________________                                    

EXAMPLES 1112-1114

Treatment of all cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-ν-lactolwith the Wittig reagent prepared from the indicated phosphonium bromidesof Table 21 below, all by the procedure of Example 1105 is productive ofthe product compounds of the table.

                  TABLE 21                                                        ______________________________________                                              Reagent phos-                                                           Ex-   phonium bromide                                                                           Product                                                     ample of Example  3,4-oxidocyclopentanol                                      ______________________________________                                        1112  1109        all cis-2-(5-carboxy-2-                                                       cis-pentenyl)-3,4-oxi-                                                        docyclopentan-1-ol                                          1113  1110        all cis-2-(7-carboxy-2-                                                       cis-heptenyl)-3,4-oxi-                                                        docyclopentan-1-ol                                          1114  1111        all cis-2-(8-carboxy-2-                                                       cis-octenyl)-3,4-oxi-                                                         docyclopentan-1-ol                                          ______________________________________                                    

EXAMPLES 1115-1117

Oxidation of the cyclopentanols indicated in Table 22 below by themethod described in Example 1108 furnishes the corresponding product3,4-oxidocyclopentanones of the table.

                  TABLE 22                                                        ______________________________________                                              Starting cyclo-                                                                           Product                                                     Ex-   pentan-1-ol of                                                                            3,4-oxidocyclopent-                                         ample Example     an-1-one                                                    ______________________________________                                        1115  1112        all cis-2-(5-carboxy-                                                         2-cis-pentenyl)-3,4-                                                          oxidocyclopentan-1-                                                           one                                                         1116  1113        all cis-2-(7-carboxy-                                                         2-cis-heptenyl)-3,4-                                                          oxidocyclopentan-1-                                                           one                                                         1117  1114        all cis-2-(8-carboxy-                                                         2-cis-octenyl)-3,4-                                                           oxidocyclopentan-1-                                                           one                                                         ______________________________________                                    

EXAMPLES 1118-1120

Alkaline treatment of the 3,4-oxidocyclopentanones of Table 23 below bythe process described in Example 1107 is productive of the4-hydroxycyclopentanones of the table.

                  TABLE 23                                                        ______________________________________                                              Starting 3,4-                                                           oxidocyclo-                                                                         Product                                                                 Ex-   pentanone of                                                                              4-hydroxycyclo-                                             ample Example     pent-2-en-1-one                                             ______________________________________                                        1118  1115        2-(5-carboxy-2-                                                               cis-pentenyl)-4-                                                              hydroxycyclo-                                                                 pent-2-en-1-one                                             1119  1116        2-(7-carboxy-2-                                                               cis-heptenyl)-                                                                4-hydroxycyclo-                                                               pent-2-en-1-one                                             1120  1117        2-(8-carboxy-2-                                                               cis-octenyl)-4-                                                               hydroxycyclo-                                                                 pent-2-en-1-one                                             ______________________________________                                    

EXAMPLES 1121-1124

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 24 belowwith dihydropyran (in the manner of Example 95) is productive of thecorresponding bis-tetrahydropyranyl ether-ester of the table.

                  TABLE 24                                                        ______________________________________                                              Starting 4-hy-                                                                droxycyclopent-                                                                           Product                                                     Ex-   2-en-l-one of                                                                             bis-tetrahydropyranyl                                       ample Example     ether-ester                                                 ______________________________________                                        1121  1107        4-tetrahydropyranyloxy-                                                       2-(6-carbotetrahydro-                                                         pyranyloxy-2-cis-hexenyl)                                                     cyclopent-2-en-1-one                                        1122  1118        4-tetrahydropyranyloxy-                                                       2-(5-carbotetrahydro-                                                         pyranyloxy-2-cis-pent-                                                        enyl)cyclopent-2-en-1-                                                        one                                                         1123  1119        4-tetrahydropyranyloxy-                                                       2-(7-carbotetrahydro-                                                         pyranyloxy-2-cis-heptenyl)-                                                   cyclopent-2-en-1-one                                        1124  1120        4-tetrahydropyranyloxy-                                                       2-(8-carbotetrahydro-                                                         pyranyloxy-2-cis-octenyl)-                                                    cyclopent-2-en-1-one                                        ______________________________________                                    

EXAMPLES 1125-1130

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 25 belowwith the indicated trialkylsilyl chloride by the method described inExample 958 is productive of the bis-trialkylsily ether-esters of thetable.

                                      TABLE 25                                    __________________________________________________________________________          Starting 4-hydroxy-                                                           cyclopentenone of                                                                       Trialkylsilyl-                                                                        Product                                               Example                                                                             Example   chloride                                                                              bis-trialkylsilyl other-ester                         __________________________________________________________________________    1125  1107      (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(6-carbotrimethyl-                                        siloxy-2-cis-hexenyl)cyclopent-2-en-1-one             1126  1118      (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(5-carbotrimethyl-                                        siloxy-2-cis-pentenyl)cyclopent-2-en-1-one            1127  1119      (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(7-carbotrimethyl-                                        siloxy-2-cis-heptenyl)cyclopent-2-en-1-one            1128  1120      (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(8-carbotrimethyl-                                        siloxy-2-cis-octenyl)cyclopent-2-en-1-one             1130  1107      dimethyliso-                                                                          4-dimethylisopropylisoloxy-2-(6-carbodi-                              propyl silyl                                                                          methylisopropylsiloxy-2-cis-hexenyl)cyclo-                            chloride                                                                              pent-2-en-1-one                                       __________________________________________________________________________

EXAMPLE 1131 Preparation of 1-oxo-2-hydroxy-bicyclo[3.3.0]oct-4-ene

A solution of 6.2 g. (50 mole) of the lactone ofcis-2-hydroxycyclopent-4-ene-1-acetic acid [P. A. Grieco, J. Org. Chem.,37, 2363 (1972)] in 350 ml. toluene (dried over molecular sieves) iscooled to -75° C. and treated dropwise under nitrogen with 84 ml. .89 Mdiisobutyl aluminum hydride (10.55 g., 74 mole) over a period of aboutone hour maintaining the temperature at -74°±2° C. The resulting clearsolution is stirred at -75° C. for two hours and poured with stirringinto a mixture of 15 ml. of concentrated hydrochloric acid and 300 ml.of ice water. The mixture is stirred whle warming to room temperature.The layers are separated and the aqueous layer is treated with salt andextracted with three small portions of ether. The combined organicportions are dried over sodium sulfate and evaporated at reducedpressure (75° C. water bath) to yield the product (homogeneous by thinlayer chromatography) as a pale yellow mobile liquid.

EXAMPLE 1132 Preparation of1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene

A solution of the sodium salt of dimethyl sulfoxide is prepared bystirring under nitrogen a mixture of 160 ml. dry dimethyl sulfoxide(dried over molecular sieve and a few pellets of calcium hydride) with6.0 g. (0.25 mole) of sodium hydride (prepaed by washing 10.5 g. of 57%sodium hydride dispersion in mineral oil with two 30 ml. portions ofhexane.) The mixture is warmed with stirring at 75° C. (oil bath) for2.5 hours.

This solution is added over about five minutes to a solution undernitrogen of 44 grams (0.1 mole) of 4-carboxybutyltriphenylphosphoniumbromide (Example 1108) in 180 ml. of dry dimethyl sulfoxide. Theresulting dark reddish brown solution is stirred for ten minutes, cooledto room temperature and treated with a solution of crude1-oxa-2-hydroxybicyclo[3.3.0]oct-4-ene (6.2 g., 50 mole) (Example 1131)in 20 ml. of anhydrous dimethyl sulfoxide. The resulting solution isstirred 16 hours and then treated with 250 ml. of ice water.

This brown solution is extracted with two portions of ether to removeneutral material then made strongly acidic with hydrochloric acid. Thesolution is extracted into four 100 ml. portions of methylene chloride.The combined methylene chloride extracts are washed with water, thenextracted with four 100 ml. portions of 5% sodium bicarbonate. Thecombined aqueous extracts are washed with methylene chloride and madeacidic to Congo Red with concentrated hydrochloric acid. The mixture isextracted with three 100 ml. portions of methylene chloride. The organicextracts are combined, dried over sodium sulfate and the solvent isevaporated at reduced pressure. The residue (an oily solid) is extractedseveral times with ether and the ethereal extracts are combined andevaporated at reduced pressure to yield the crude product as a dark oil.The product is purified by chromatographs on silica gel, eluting withether. The product is a colorless liquid.

EXAMPLE 1133 Preparation of2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one

A solution of 3.2 g. (0.5 mole) of1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene (Example 1132) in60 ml. of reagent acetone is treated dropwise with a total of 6 ml. of8N chromic acid in sulfuric acid at 0° C. The oxidation is rather slow.The resulting mixture is dissolved in 200 ml. of water and the solutionis extracted with six 50 ml. portions of ether. The combined etherealextracts are dried over sodium sulfate and the solvent is evaporated atreduced pressure to yield the product as a yellow oil.

EXAMPLE 1134 Preparation of2-(6-carboxy-2-cis-hexenyl)cyclopent-2-en-1-one

A solution of 3 g. of crude2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one (Example 1133) in 100ml. of 2% sodium hydroxide is stirred at 80° C. under nitrogen for 1.5hours. The cooled solution is acidified to Congo Red and extracted intoether. The ethereal extracts are dried over sodium sulfate andevaporated at reduced pressure to afford the product.

EXAMPLES 1135-1137

Treatment of 1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-ene by the proceduredescribed in Example 1132 with the ylids derived from the phosphoniumbromides listed in Table 26 below furnishes the product1-hydroxy-cyclopent-3-enes of the table.

                  TABLE 26                                                        ______________________________________                                                          Product                                                           Starting phos-                                                                            1-hydroxy-2-(ω-carboxy-                               Ex-   phonium bromide                                                                           2-cis-alkenyl)cyclopent-                                    ample of Example  3-enes                                                      ______________________________________                                        1135  1109        1-hydroxy-2-(5-carboxy-                                                       2-cis-pentenyl)cyclo-                                                         pent-3-ene                                                  1136  1110        1-hydroxy-2-(7-carboxy-                                                       2-cis-heptenyl)cyclo-                                                         pent-3-ene                                                  1137  1111        1-hydroxy-2-(8-carboxy-                                                       2-cis-octenyl)cyclo-                                                          pent-3-ene                                                  ______________________________________                                    

EXAMPLES 1138-1140

Oxidation of the 1-hydroxycyclopent-3-enes listed in Table 27 below bythe procedure described in Example 1133 is productive of the productcyclopent-3-en-1-ones of the table.

                  TABLE 27                                                        ______________________________________                                              Starting 1- Product                                                           hydroxycyclo-                                                                             2-(ω-carboxy-2-cis-                                   Ex.   pent-3-ene of                                                                             alkenyl)cyclopent-3-                                        ample Example     en-1-one                                                    ______________________________________                                        1138  1135        2-(5-carboxy-2-cis-                                                           pentenyl)cyclopent-3-                                                         en-1-one                                                    1139  1136        2-(7-carboxy-2-cis-                                                           heptenyl)cyclopent-3-                                                         en-1-one                                                    1140  1137        2-(8-carboxy-2-cis-                                                           octenyl)cyclopent-3-                                                          en-1-one                                                    ______________________________________                                    

EXAMPLES 1141-1143

Base treatment according to the procedure described in Example 1134 ofthe cyclopent-3-ene-1-ones listed in Table 28 below is productive of theproduct cyclopent-2-en-1-ones of the table.

                  TABLE 28                                                        ______________________________________                                              Starting 2-(ω-                                                          carboxy-2-cis- Product                                                        alkenyl)cyclo- 2-(ω-carboxy-2-cis-                                Ex-   pent-3-ene-1-  alkenyl)cyclopent-                                       ample one of Example 2-en-1-one                                               ______________________________________                                        1141  1138           2-(5-carboxy-2-cis-                                                           pentenyl)cyclopent-                                                           2-en-1-one                                               1142  1139           2-(7-carboxy-2-cis-                                                           heptenyl)cyclopent-                                                           2-en-1-one                                               1143  1140           2-(8-carboxy-2-cis-                                                           octenyl)cyclopent-                                                            en-en-1-one                                              ______________________________________                                    

EXAMPLES 1144-1146

Treatment of the listed 2-(ω-carboxy-2-cis-alkenyl)cyclopent-2-en-1-oneof Table 29 below with diazomethane in the usual manner is productive ofthe product methyl esters of the table.

                  TABLE 29                                                        ______________________________________                                                             Product                                                        Starting car-  2-(ω-carbomethoxy-2-cis-                           Ex-   boxylic acid   alkenyl)cyclopent-2-en-                                  ample of Example     1-one                                                    ______________________________________                                        1144  1141           2-(5-carbomethoxy-2-cis-                                                      pentenyl)cyclopent-2-en-                                                      1-one                                                    1145  1142           2-(7-carbomethoxy-2-cis-                                                      heptenyl)cyclopent-2-en-                                                      1-one                                                    1148  1143           2-(8-carbomethoxy-2-cis-                                                      octenyl)cyclopent-2-en-                                                       1-one                                                    ______________________________________                                    

EXAMPLES 1147-1149

Treatment by the procedure of Example 120 of the cyclopentenones listedin Table 30 below with lithiumdiisobutylmethyl-(3-triphenylmethoxy-1-trans-5-cis-octadienyl) alanate,also prepared by the procedure of Example 120 from3-triphenylmethoxy-cis-5-en-octyne-1 (Example 139), diisobutylaluminumhydride and methyl lithium, followed by hydrolysis of the intermediate15-triphenylmethoxy derivatives by treatment with aceticacid-tetrahydrofuran-water (4:2:1) in the manner of Example 121, andthen by saponification of the intermediate methyl esters by the processdescribed in Example 122 is productive of the product prostatrienoicacids of the table.

                  TABLE 30                                                        ______________________________________                                              Starting 2-(ω-                                                          carbomethoxy-2-                                                                              Product                                                        cis-alkenyl)-  9-oxo-15-hydroxy-5-                                      Ex-   cyclopent-2-en-                                                                              cis,13-trans,17-cis-                                     ample 1-one of Example                                                                             prostatrienoic acids                                     ______________________________________                                        1147  1144           9-oxo-4-nor-15-hydroxy-                                                       5-cis-13-trans-17-                                                            cis-prostatrienoic                                                            acid                                                     1148  1145           9-oxo-4a-homo-15-hydro-                                                       xy-5-cis-13-trans-17-                                                         cis-prostatrienoic                                                            acid                                                     1149  1146           9-oxo-4a-bishomo-15-hy-                                                       droxy-5-cis-13-trans-                                                         17-cis-prostatrienoic                                                         acid                                                     ______________________________________                                    

EXAMPLES 1150-1159

Treatment of the ether-ester blocked 4-oxycyclopent-2-en-1-ones listedin Table 31 below with lithiumtrimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl] according to theprocedure described in Example 960 is productive of the9-oxo-11α,15-dihydroxy-5-cis,13-trans-prostadienoic acids of the tableas well as the corresponding 15-epi derivatives, separable from thelisted 15-normal derivatives by chromatography.

                  TABLE 31                                                        ______________________________________                                              Starting blocked                                                              4-oxycyclopent-                                                                              9-oxo-11α,15-dihydroxy-                            Ex-   2-en-1-one of  5-cis,13-trans-pros-                                     ample Example        tadienoic acids                                          ______________________________________                                        1150  1121           9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                         1151  1125           9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                         1152  1130           9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                         1153  1122           9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans-                                                         prostadienoic acid                                       1154  1126           9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans-                                                         prostadienoic acid                                       1155  1123           9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-trans-                                                       prostadienoic acid                                       1156  1127           9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-trans-                                                       prostadienoic acid                                       1158  1124           9-oxo-11α,15-dihydroxy-                                                 4a,4b-homo-5-cis,13-                                                          trans-prostadienoic                                                           acid                                                     1159  1128           9-oxo-11α,15-dihydroxy-                                                 4a,4b-homo-5-cis,13-                                                          trans-prostadienoic                                                           acid                                                     ______________________________________                                    

EXAMPLES 1160-1169

Treatment by the procedure described in Example 123 of the ether-esterblocked 4-oxycyclopent-2-en-1-ones listed in Table 32 below with lithiumdiisobutylmethyl(3-triphenylmethoxy-1-trans-5-cis-octadienyl)alanate,prepared from 3-triphenylmethoxy-cis-5-en-octyne-1- (Example 139) by theprocedure of Example 120, followed by the cleavage of blocking groupsand isolation of products by the method described in Example 124 isproductive of the9-oxo-11α,15-dihydroxy-5-cis,13-trans,17-cis-prostatrienoic acids of thetable; also formed are the corresponding 15-epi derivatives which areseparable by chromatography from the listed 15-normal derivatives.

                  TABLE 32                                                        ______________________________________                                                Starting blocked                                                                             Product                                                        4-oxycyclopent-                                                                              9-oxo-11α,15-dihydroxy-                          Ex-     2-en-1-one of  5-cis,13-trans,17-cis-                                 ample   Example        prostatrienoic acids                                   ______________________________________                                        1160    1121           9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-                                                            cis-prostatrienoic                                                            acid (prostaglandin E.sub.3)                           1161    1125           9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-cis-                                                        prostatrienoic acid                                                           (prostaglandin E.sub.3)                                1162    1130           9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-cis-                                                        prostatrienoic acid                                                           (prostaglandin E.sub.3)                                1163    1122           9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans,                                                         17-cis-prostatrienoic                                                         acid                                                   1164    1126           9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans,                                                         17-cis-prostatrienoic                                                         acid                                                   1165    1123           9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-                                                             trans,17-cis-prosta-                                                          trienoic acid                                          1166    1127           9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-                                                             trans,17-cis-prosta-                                                          trienoic acid                                          1168    1124           9-oxo-11α,15-dihydroxy-                                                 4a,4b-bishomo-5-cis,                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                          1169    1128           9-oxo-11α,15-dihydroxy-                                                 4a,4b-bishomo-5-cis-                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                          ______________________________________                                    

EXAMPLE 1170 Preparation of9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoic acid

Treatment in the manner described in Example 733 of4-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxy-2-cis-hexenyl)cyclopent-2-en-1-one(Example 1121) with the Grignard reagent prepared from magnesium and1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) also asdescribed in Example 733 in the presence of cuprous iodidetri-n-butylphosphine complex is productive after chromatography ofprostaglandin E₂ and 9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoicacid.

EXAMPLES 1171and 1172

Treatment of the two 9-oxo derivative listed in Table 33 below withlithium perhydro-9b-boraphenalylhydride in the manner described inExample 737 furnishes the indicated 9α,15-dihydroxy-13-cis-prostenoicacids.

                  TABLE 33                                                        ______________________________________                                                  Starting 9-oxo-                                                                             Product                                               Ex-       derivative of 9α,15-dihydroxy-13-cis-                         ample     Example       prostenoic acids                                      ______________________________________                                        1171       736          9α,15-dihydroxy-13-cis-                                                 prostenoic acid                                       1172      1170          9α,15-dihydroxy-5-cis-                                                  prostadienoic acid                                    ______________________________________                                    

EXAMPLE 1173 Preparation of1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

To an ice cooled solution of 3.5 g. (50 moles) of 2-methyl-2-butene in25 ml. of tetrahydrofuran under an inert atmosphere is added 25 ml. of 1M diborane in tetrahydrofuran dropwise over 10 minutes. The mixture isstirred at 0°-5° C. for 2 hours and then the solvent is removed undervacuum. The residue is dissolved in 20 ml. of carbon tetrachloride andto the resulting solution cooled to 0° C. is added a solution of 5.25 g.(22 mole) of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995)in 10 ml. of carbon tetrachloride over 10 minutes. The cooling bath isremoved and the mixture is allowed to stir at ambient temperature for1.5 hours. The mixture is cooled to 0° C. and a solution of 3.52 g. (22moles) of bromine in 15 ml. of carbon tetrachloride is added over 10minutes. The cooling bath is removed and the mixture is refluxed for 6hours under an inert atmosphere. The mixture is cooled and poured intodilute sodium hydroxide solution. The organic phase is washed with waterand saturated brine, dried (Na₂ SO₄), and evaporated. The residue ischromatographed upon silica gel and the title compound is isolated with5% ethyl acetate in benzene.

EXAMPLE 1174 Preparation of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol

A mixture of 3.19 g. (10 moles) of1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example1173) and 90 ml. of 3:1:1 tetrahydrofuran-acetic acid-water is stirredat ambient temperature for 20 hours. The solvent is evaporated in vacuoand the residue is chromatographed on silica gel. The title compound isisolated using 10-20% ethyl acetate in benzene.

EXAMPLE 1175 Preparation of1-bromo-4,4-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 1.88 g. (8 moles) of1-bromo-4,4-dimethyl-trans-1-octen-3-ol (Example 1174) with 2.58 g. (8moles) of triphenylmethyl bromide in 20 ml. of pyridine and purificationof Florisil®, all as described in Example 728 gives the title compound.

EXAMPLE 1176 Preparation of1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

Treatment of 7.15 g. (30 moles) of5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) with 33 molesof disiamylborane in carbon tetrachloride followed by 30 moles ofbromide in carbon tetrachloride, refluxing the resulting mixture, andisolation by chromatography on silica gel, all as described in Example1173 gives the title compound.

EXAMPLE 1177 Preparation of 1-bromo-5,5-dimethyl-trans-1-octen-3-ol

Treatment of 7.35 g. (23 moles ) of1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octane (Example1176) with 200 ml. of 3:1:1 tetrahydrofuran-acetic acid-water andpurification on silica gel all as described in Example 1174 gives thetitle compound.

EXAMPLE 1178 Preparation of1-bromo-5,5-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 3.53 g. (15 moles) of1-bromo-5,5-dimethyl-trans-1-octen-3-ol (Example 1177) with 4.83 g. (15moles) of triphenylmethyl bromide in 35 ml. of pyridine and purificationon Florisil®, all as described in Example 728 gives the title compound.

EXAMPLE 1179 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

To a mixture of 0.650 g. (16.91 mole) of sodium borohydride and 3.17 g.(45.2 moles) of 2-methyl-2-butene in 40 ml. of diglyme cooled at -5° C.under an inert atmosphere is added over 15 minutes 3.24 g. (22.6 moles)of boron trifluoride ethereate and the resulting mixture is stirred at0° C. for 2 hours. To this mixture is then added over 5 minutes 8.32 g.(22.6 moles) of 3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. ofdiglyme, the cooling bath is removed, and the mixture is stirred atambient temperatures for 1.5 hours. The mixture is cooled to 0° C. and6.0 g. of finely divided anhydrous trimethylamine oxide is added over 10minutes. The cooling bath is removed and the mixture is stirred atambient temperatures for 0.5 hour. The mixture is then poured into 200ml. of 15% sodium hydroxide solution, a solution of 16 g. (63 moles) ofiodine in 20 ml. of tetrahydrofuran is added immediately, and theresulting mixture is stirred for 0.5 hour. The organic phase isseparated and the aqueous phase is washed with ether. The combinedorganic phase and washings are decolorized with 5% sodium thiosulfatesolution, washed with saturated brine, dried (Na₂ SO₄), and evaporated.The residue is dry-columned chromatographed upon alumina using hexane aseluent and the title compound is isolated as an oil.

EXAMPLE 1180 Preparation of 3-triphenylmethoxy-cis-oct-5-en-1-yne

Treatment of 22 g. of cis-oct-5-en-1-yne-3-ol, prepared according to theprocedure of J. Fried, C. W. Lin, J. C. Sih, P. Delvon, G. F. Cooper, J.Amer. Chem. Soc., 94, 4342 (1972), with 58 g. of triphenylmethyl bromidein 100 ml. of pyridine and purification on Florisil®, all as describedin Example 728 gives the title compound.

EXAMPLE 1181 Preparation of1-iodo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 20 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne with 55moles of disiamylborane in diglyme, followed by trimethylamine-oxide,aqueous sodium hydroxide, and iodine, and purification of alumina, allas described in Example 1179, gives the title compound.

EXAMPLE 1182 Preparation of1-bromo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 15 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne (Example1180) with 41 moles of disiamylborane in tetrahydrofuran, replacing thesolvent with carbontetrachloride, addition of 41 moles of bromine, andrefluxing the mixture, all as described in Example 1173, andpurification of the material upon Florisil® as described in Example 728gives the title compound.

EXAMPLE 1183 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-decane

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) withdisamylborane, trimethylamine oxide and iodine by the proceduredescribed in Example 1179 is productive of the subject compound.

EXAMPLE 1184 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) withdisiamylborane, trimethylamine oxide and iodine by the process describedin Example 1179 is productive of the subject compound.

EXAMPLE 1185 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) withdisiamylborane and the bromide by the procedure described in Example1173 is productive of the title compound.

EXAMPLE 1186 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) withdisiamylborane and the bromide by the procedure described in Example1173 is productive of the title compound.

EXAMPLE 1187 Preparation of the Grignard reagent of1-bromo-3-triphenylmethoxy-trans-1-octene at 33° C.

To a slurry of 0.585 g. (0.0241 g. atom) of magnesium and 5 ml. oftetrahydrofuran under an argon atmosphere is added 2 ml. of a solutionof 7.536 (0.0168 mole) of 1-bromo-3-triphenylmethoxy-trans-1-octene(Example 728) in 10 ml. of tetrahydrofuran. The mixture is warmed at 35°C. and reaction is initiated with 1 drop of methyl iodide. The reactionis allowed to exotherm to 37° C. and then to cool to 33° C. whereuponthe remainder of the halide is added at a rate to maintain 33° C. Aftercomplete addition of the halide, the mixture is stirred at 33° C. for 1hour and is separated from the excess magnesium to yield atetrahydofuran solution of the title Grignard reagent.

EXAMPLE 1188 Preparation of 11-deoxy-8β-methyl-prostaglandin E₁ methylester, 11-deoxy-8α-methyl-8-iso-prostaglandin E₁ methyl ester, methyl15-hydroxy-8α -methyl-9-oxo-13-cis-prostenoate, and methyl15-hydroxy-8α-methyl-9-oxo-8-iso-13-cis-prostenoate

The Grignard reagent, prepared as described in Example 1187 from 0.585g. of magnesium, 7.536 g. of 1-bromo-3 -triphenylmethoxy-trans-1-octene(Example 728), and 10 ml. of tetrahydrofuran, is added to an ice cooledsolution of 3.76 g. of 2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example83) and 0.305 g. of copper (I) iodide-tri-n-butylphosphine complex in 10ml. of tetrahydrofuran over 10 minutes under an inert atmosphere. Themixture is stirred with cooling for 0.5 hour and to it is then added 46g. of methyl iodide. The cooling bath is removed and the mixture isstirred at ambient temperature for 48 hours. The mixture is poured intosaturated ammonium chloride solution and is extracted into ether. Theorganic phase is washed with saturated brine and is evaporated. Theresidue is heated to 80° C. with 100 ml of 80% aqueous acetic acid for0.5 hour and the mixture is then evaporated to dryness. The residue isdry-column chromatography upon silica gel using 4:1 benzene-ethylacetate as eluent to afford a mixture of11-deoxy-8β-methyl-prostaglandin E₁ methyl ester and11-deoxy-8α-methyl-8-iso-prostaglandin E₁ methyl ester and a mixture ofmethyl 15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoate and methyl15-hydroxy-8α-methyl-9-oxo-8-iso-13-cis-prostenoate. Further separationof the 8β and 8α isomers is accomplished by a combination of partitionchromatography and thin layer chromatography.

EXAMPLES 1190-1205

Treatment by the procedure of Example 1188 of the cyclopentenones listedin Table 34 below with the Grignard reagent, prepared as described inExample 1187 from the listed 1-bromo-3-triphenylmethoxy-1-trans-alkenes,and then with methyl iodide furnishes the product 8α and 8β methylprostenoates of the table. The products are all obtained via thecorresponding 15-O-triphenylmethyl derivatives, which are hydrolyticallycleaved as described in Example 1188.

                                      TABLE 34                                    __________________________________________________________________________                    Starting 1-bromo-3-                                                           triphenylmethoxy-1-                                                Starting cycloalkenene                                                                   trans-alkene of                                               Example                                                                            of Example Example   Product 8-alkyl prostenoates                        __________________________________________________________________________    1190  13        1175      ethyl 8-β-methyl-9-oxo-15-hydroxy-16,16-                                 dimethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-                                 dimethyl-8-iso-13-trans-prostenoate                                           ethyl 8βmethyl-9-oxo-15-hydroxy-16,16-                                   dimethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-                                 dimethyl-8-iso-13-cis-prostenoate                   1191 13         1178      ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-                                  dimethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                 dimethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-                                  dimethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                 dimethyl-8-iso-13-cis-prostenoate                   1192 13         1182      ethyl 8β-methyl-9-oxo-15-hydroxy-13-trans,                               N                                                                             17-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-13-                              O                                                                             trans,17-cis-prostadienoate                                                   ethyl 8β-methyl-9-oxo-15-hydroxy-13-cis,                                 17-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 13-cis,17-cis-prostadienoate                        1193 13         1185      ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               O                                                                             13-trans-prostenoate                                                          ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-                              c                                                                             8-iso-13-trans-prostenoate                                                    ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               t                                                                             13-cis-prostenoate                                                            ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-20-                              1                                                   ethyl-13-cis-prostenoate                                                      1194 84         1186      decyl 8β-methyl-9-oxo-15-hydroxy-20-           methyl-13-trans-prostenoate                                                                             decyl 8α-methyl-9-oxo-15-hydroxy-20-                                    methyl-8-iso-13-trans-prostenoate                                             decyl 8β-methyl-9-oxo-15-hydroxy-20-                                     methyl-13-cis-prostenoate                                                     decyl 8α-methyl-9-oxo-15-hydroxy-20-                                    methyl-8-iso-13-cis-prostenoate                     1195 23          728      ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-                                  bishomo-13-trans-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-                                 bishomo-8-iso-trans-prostenoate                                               ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-                                  bishomo-13-cis-prostenoate                                                    ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-                                 bishomo-8-iso-13-cis-prostenoate                    1196 31         1185      ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-                                   bisethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-                                  bisethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-                                   bisethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-                                  bisethyl-8-iso-13-cis-prostenoate                   1197 46         1175      ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,                               0                                                                             16-dimethyl-13-trans-prostenoate                                              ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,                              N                                                                             16-dimethyl-8-iso-13-trans-prostenoate                                        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,                               o                                                                             16-dimethyl-13-cis-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,                              v                                                                             16-dimethyl-8-iso-13-cis-prostenoate                1198 46         1182      ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-                                  13-trans,17-cis-prostadienoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 8-iso-13-trans,17-cis-prostadienoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-                                  13-cis,17-cis-prostadienoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 8-iso-13-cis,17-cis-prostadienoate                  1199 53         1186      ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-                                  20-methyl-13-trans-prostadienoate                                             ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                 20-methyl-8-iso-13-trans-prostadienoate                                       ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-                                  20-methyl-13-cis-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                 20-methyl-8-iso-13-cis-prostenoate                  1200 70         1178      ethyl-8β-methyl-9-oxo-15-hydroxy-2-fluoro-                               1                                                                             17,17-dimethyl-13-trans-prostenoate                                           ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluoro-                              1                                                                             17,17-dimethyl-8-iso-13-trans-prostenoate                                     ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluoro-                               D                                                                             17,17-dimethyl-13-cis-prostenoate                                             ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluoro-                              N                                                                             17,17-dimethyl-8-iso-13-cis-prostenoate             1201 111         728      ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-                               O                                                                             13-trans-prostenoate                                                          ethyl 8α-methyl-9-oxo-15-hydroxy-10α                              -homo-                                              8-iso-13-trans-prostenoate                                                                              ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-                               c                                                                             13-cis-prostenoate                                                            ethyl 8α-methyl-9-oxo-15-hydroxy-10a-homo-                              1                                                                             8-iso-13-cis-prostenoate                            1202 79         1186      ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-                               2                                                                             20-methyl-13-trans-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-                              20-methyl-8-iso-13-trans-prostenoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-                               20-methyl-13-cis-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-                              20-methyl-8-iso-13-cis-prostenoate                  1203 900        1182      methyl 8β-methyl-9-oxo-15-hydroxy-                                       5-cis,13-trans,17-cis-prostenoate                                             methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                5-cis,13-trans,17-cis-prostatrienoate                                         methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                 13-cis,17-cis-prostatrienoate                                                 methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                5-cis,13-cis,17-cis-prostatrienoate                 1204 900         728      ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-trans-prostadienoate                                                       ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 5-cis,13-trans-prostadienoate                                                 ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 5-cis,13-cis-prostadienoate                         1205 900        1185      ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               5-cis,13-trans-prostadienoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-                              8-iso-5-cis,13-trans-prostadienoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               5-cis,13-cis-prostadienoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-                              8-iso-5-cis,13-cis-prostadienoate                   __________________________________________________________________________

EXAMPLES 1206-1273

Teatment of the designated 9-oxo-prostenoic acid and ester derivativeslisted in Table 35 below with sodium borohydride in ethanol as describedin Example 257 gives the product 9α and 9β hydroxy derivatives of thetable, which are separable by standard chromatographic techniques.

                  TABLE 35                                                        ______________________________________                                        Ex-     Starting 9-oxo-                                                                              Product 9-hydroxy                                      ample   derivative     derivatives                                            ______________________________________                                        1206    11-deoxy-8β-                                                                            11-deoxy-8β-methyl-pros-                                  methyl-prosta- taglandin F.sub.1 α and F.sub.1 β                   glandin E.sub.1 meth-                                                                        methyl esters                                                  yl ester                                                                      (Example 1188)                                                        1207    11-deoxy-8α-                                                                           11-deoxy-8α-methyl-8-iso-                                methyl-8-iso-  prostaglandin F.sub.1 α and                              prostaglandin  F.sub.1 β methyl esters                                   E.sub.1 methyl ester                                                          (Example 1188)                                                        1208    methyl 15-hy-  methyl 9α/β, 15-di-                                 droxy-8β-meth-                                                                          hydroxy-8β-methyl-13-                                     yl-9-oxo-13-   cis-prostenoates                                               cis-prostenoate                                                               (Example 1188)                                                        1209    methyl 15-hy-  methyl 9α/β, 15 dihydroxy                           droxy-8α-meth-                                                                         8α-methyl-8-iso-13-cis-                                  yl-9-oxo-13-   prostenoates                                                   cis-prosteno-                                                                 ate (Example                                                                  1188)                                                                 1210    ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-   dihydroxy-16,16-dimeth-                                        hydroxy-16-    yl-13-trans-prosteno-                                          16-dimethyl-   ates                                                           13-trans-                                                                     prostenoate                                                                   (Example 1190)                                                        1211    ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-   dihydroxy-16,16-dimeth-                                        hydroxy-16,-   yl-8-iso-13-trans-pros-                                        16-dimethyl-   tenoates                                                       8-iso-13-                                                                     trans-prosten-                                                                oate (Example                                                                 1190)                                                                 1212    ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                              dihydroxy-16,16-dimeth-                                        droxy-16,16-   yl-13-cis-prostenoates                                         dimethyl-13-                                                                  cis-prosteno-                                                                 ate (Example                                                                  1190)                                                                 1213    ethyl 8α -meth-                                                                        ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-   dihydroxy-16,16-dimeth-                                        hydroxy-16,-   yl-8-iso-13-cis-prosten-                                       16-dimethyl-8- oates                                                          iso-13-cis-                                                                   prostenoate                                                                   (Example 1190)                                                        1214    8β-methyl-9-                                                                            ethyl 8β-methyl-9α/β,15-                       oxo-15-hydrox- dihydroxy-17,17-dimeth-                                        y-17,17-dimeth-                                                                              yl-13-trans-prostenoates                                       yl-13-trans-                                                                  prostenoate                                                                   (Example 1191)                                                        1215    ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-   dihydroxy-17,17-dimeth-                                        hydroxy-17,17- yl-8-iso-13-trans-pros-                                        dimethyl-8-    tenoates                                                       iso-13-trans-                                                                 prostenoate                                                                   (Example 1191)                                                        1216    ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-   dihydroxy-17,17-dimeth-                                        hydroxy-17,17- yl-13-cis-prostenoates                                         dimethyl-13-                                                                  cis-prosteno-                                                                 ate (Example                                                                  1191)                                                                 1217    ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-hy-                                                                              dihydroxy-17,17-dimeth-                                        droxy-17,17-di-                                                                              yl-8-iso-13-cis-prosten-                                       methyl-8-iso   oates                                                          13-cis-prosten-                                                               oate (Example                                                                 1191)                                                                 1218    ethyl-8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                              dihydroxy-13-trans,17-                                         droxy-13-trans-                                                       cis-prostadienoates                                                                   17-cis-prosta-                                                                dienoate (Exam-                                                               ple 1192)                                                             1219    ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-hy-                                                                              dihydroxy-8-iso-13-trans-                                      droxy-8-iso-13-                                                                              17-cis-prostadienoates                                         trans,17-cis-                                                                 prostadienoate                                                                (Example 1192)                                                        1220    ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                              dihydroxy-13-cis,17-                                           droxy-13-cis,- cis-prostadienoates                                            17-cis-prostadi-                                                              enoate (Example                                                               1192)                                                                 1221    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-8-iso-13-cis-                                        droxy-8-iso-13-                                                                              17-cis-prostadienoates                                         cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1192)                                                             1222    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-ethyl-13-                                         droxy-20-ethyl-13-                                                                           trans-prostenoates                                             trans-prosteno-                                                               ate (Example 1193)                                                    1223    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-ethyl-8-                                          droxy-20-ethyl-8-                                                                            iso-13-trans-prosteno-                                         iso-13-trans-  ates                                                           prostenoate                                                                   (Example 1193)                                                        1224    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-ethyl-13-                                         droxy-20-ethyl-13-                                                                           cis-prostenoates                                               cis-prostenoate                                                               (Example 1193)                                                        1225    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-ethyl-8-                                          droxy-20-ethyl-                                                                              iso-13-cis-prostenoates                                        8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1193)                                                        1226    decyl 8β-methyl-                                                                        decyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-methyl-13-                                        droxy-20-methyl-                                                                             trans-prostenoates                                             13-trans-pros-                                                                tenoate (Example                                                              1194)                                                                 1127    decyl 8α-methyl-                                                                       decyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-methyl-8-                                         droxy-20-methyl-                                                                             iso-13-trans-prosteno-                                         8-iso-13-trans-                                                                              ates                                                           prostenoate                                                                   (Example 1194)                                                        1128    decyl 8β-methyl-                                                                        decyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-methyl-13-                                        droxy-20-methyl-                                                                             cis-prostenoates                                               13-cis-prosten-                                                               oate (Example                                                                 1194)                                                                 1229    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-methyl-8-                                         droxy-20-methyl-                                                                             iso-13,cis-prostenoates                                        8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1194)                                                        1230    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-13-trans-prosteno-                                        homo-13-trans- ates                                                           prostenoate                                                                   (Example 1195)                                                        1231    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-8-iso-13-trans-                                           homo-8-iso-13- prostenoates                                                   trans-prosteno-                                                               ate (Example                                                                  1195)                                                                 1232    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-13-cis-prosteno-                                          homo-13-cis-pros-                                                                            ates                                                           tenoate (Example                                                              1195)                                                                 1233    ethyl 8α-methyl-                                                                       ethyl 8α -methyl-9α/β,15-                     9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-8-iso-13-cis-pros-                                        homo-8-iso-13- tenoates                                                       cis-prostenoate                                                               (Example 1195)                                                        1234    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-13-trans-prosteno-                                       ethyl-13-trans-                                                                              ates                                                           prostenoate                                                                   (Example 1196)                                                        1235    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-8-iso-13-trans-                                          ethyl-8-iso-13-                                                                              prostenoates                                                   trans-prosteno-                                                               ate (Example                                                                  1196)                                                                 1236    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihdyroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-13-cis-prosteno-                                         ethyl-13-cis-  ates                                                           prostenoate                                                                   (Example 1196)                                                        1237    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-8-iso-13-cis-pros-                                       ethyl-8-iso-13-                                                                              tenoates                                                       cis-prostenoate                                                               (Example 1196)                                                        1238    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-13-trans-pros-                                        16-dimethyl-13-                                                                              tenoates                                                       trans-prosteno-                                                               ate (Example                                                                  1197)                                                                 1239    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-8-iso-13-trans-                                       16-dimethyl-8- prostenoates                                                   iso-13-trans-                                                                 prostenoate                                                                   (Example 1197)                                                        1240    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-13-iso-pros-                                          16-dimethyl-13-                                                                              tenoates                                                       cis-prostenoate                                                               (Example 1197)                                                        1241    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-8-iso-13-cis-                                         16-dimethyl-8- prostenoates                                                   iso-13-cis-                                                                   prostenoate                                                                   (Example 1197)                                                        1242    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-13-                                            droxy-3-oxa-13-                                                                              trans,17-cis-prostadi-                                         trans,17-cis-  enoates                                                        prostadienoate                                                                (Example 1198)                                                        1243    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-3-oxa-8-iso-                                         droxy-3-oxa-8- 13-trans,17-cis-prosta-                                        iso-13-trans,- dienoates                                                      17-cis-prostadi-                                                              enoate (Example                                                               1198)                                                                 1244    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-13-cis-                                        droxy-3-oxa-13-                                                                              17-cis-prostadienoates                                         cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1198)                                                             1245    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-3-oxa-8-iso-                                         droxy-3-oxa-8-iso-                                                                           13-cis,17-cis-prosta-                                          13-cis,17-cis- dienoates                                                      prostadienoate                                                                (Example 1198)                                                        1246    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-13-trans-pros-                                          methyl-13-trans-                                                                             tenoates                                                       prostenoate                                                                   (Example 1199)                                                        1247    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-8-iso-13-trans-                                         methyl-8-iso-13-                                                                             prostenoates                                                   trans-prosteno-                                                               ate (Example 1199)                                                    1248    ethyl 8β-methyl-                                                                        ethyl 6β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-13-cis-prosteno-                                        methyl-13-cis- ates                                                           prostenoate                                                                   (Example 1199)                                                        1249    ethyl 8β-methyl-                                                                        ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-8-iso-13-cis-                                           methyl-8-iso-  prostenoates                                                   13-cis-prosteno-                                                              ate (Example                                                                  1199)                                                                 1250    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-fluoro-17,-                                        droxy-2-fluoro-                                                                              17-dimethyl-13-trans-                                          17,17-dimethyl-                                                                              prostenoates                                                   13-trans-prosten-                                                             oate (Example                                                                 1200)                                                                 1251    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2-fluoro-17,-                                        droxy-2-fluoro-                                                                              17-dimethyl-8-iso-13-                                          17,17-dimethyl-                                                                              trans-prostenoates                                             8-iso-13-trans-                                                               prostenoate                                                                   (Example 1200)                                                        1252    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-fluro-17,-                                         droxy-2-fluoro-17,                                                                           17-dimethyl-13-cis-pros-                                       17-dimethyl-13-                                                                              tenoates                                                       cis-prostenoate                                                               (Example 1200)                                                        1253    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2-fluoro-17,-                                        droxy-2-fluoro-                                                                              17-dimethyl-8-iso-13-                                          17,17-dimethyl-                                                                              cis-prostenoates                                               8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1200)                                                        1254    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-10α-homo-13-                                   droxy-10α-homo-13-                                                                     trans-prostenoates                                             trans-prosteno-                                                               ate (Example                                                                  1201)                                                                 1255    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α-β,15-                      9-oxo-15-hy-   dihydroxy-10α-homo-8-                                    droxy-10α-homo-8                                                                       iso-13-trans-prosteno-                                         iso-13-trans-  ates                                                           prostenoate                                                                   (Example 1201)                                                        1256    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-10α-homo-13-                                   droxy-10α-homo-                                                                        cis-prostenoates                                               13-cis-prosten-                                                               oate (Example                                                                 1201)                                                                 1257    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-10α-homo-8-                                    droxy-10α-homo-8-                                                                      iso-13-cis-prostenoates                                        iso-13-cis-pros-                                                              tenoate (Example                                                              1201)                                                                 1258    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-13-trans-prosten-                                       20-methyl-13-  oates                                                          trans-prosteno-                                                               ate (Example                                                                  1202)                                                                 1259    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-8-iso-13-trans-                                         20-methyl-8-iso-                                                                             prostenoates                                                   13-trans-pros-                                                                tenoate (Example                                                              1202)                                                                 1260    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-13-cis-prosteno-                                        20-methyl-13-cis-                                                                            ates                                                           prostenoate                                                                   (Example 1202)                                                        1261    ethyl 8α-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-8-iso-13-cis-                                           20-methyl-8-iso-                                                                             prostenoates                                                   13-cis-prosteno-                                                              ates (Example                                                                 1202)                                                                 1262    methyl 8β-methyl-                                                                       methyl 8β-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-5-cis,13-                                            droxy-5-cis,13-                                                                              trans,17-cis-prostatri-                                        trans,17-cis-pros-                                                                           enoates                                                        tatrienoate                                                                   (Example 1203)                                                        1263    methyl 8α-methyl-                                                                      methyl 8α-methyl-9α/β,15-                     9-oxo-15-hy-   dihydroxy-8-iso-5-cis,-                                        droxy-8-iso-5- 13-trans,17-cis-prosta-                                        cis,13-trans-17,                                                                             trienoates                                                     cis-prostatri-                                                                enoate                                                                        (Example 1203)                                                        1264    methyl 8β-methyl-                                                                       methyl 8β-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-5-cis,13-                                         droxy-5-cis,13-                                                                              cis,17-cis-prostatri-                                          cis,17-cis-pros-                                                                             enoates                                                        tatrienoate                                                                   (Example 1203)                                                        1265    methyl 8α-methyl-                                                                      methyl 8α-methyl-9α/β,15-                     9-oxo-15-hy-   dihydroxy-8-iso-5-cis,-                                        droxy-8-iso-5- 13-cis,17-cis-prostatri-                                       cis,13-cis,17- enoates                                                        cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                 1266    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,-                         9-oxo-15-hy-   15-dihydroxy-5-cis,13-                                         droxy-5-cis,13-                                                                              trans-prostadienoates                                          trans-prostadi-                                                               enoates (Example                                                              1204)                                                                 1267    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-8-iso-5-                                          droxy-8-iso-5- cis,13-trans-prosta-                                           cis,13-trans-  dienoates                                                      prostadienoate                                                                (Example 1204)                                                        1268    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-α/β,-                          9-oxo-15-hy-   15-dihydroxy-5-cis,13-                                         droxy-5-cis,13-                                                                              cis-prostadienoates                                            cis-prostadien-                                                               oate (Example                                                                 1204)                                                                 1269    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-8-iso-5-                                          droxy-8-iso-5- cis,13-cis-prostadien-                                         cis,13-cis-    oates                                                          prostadienoate                                                                (Example 1204)                                                        1270    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,-                         9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-                                                                              5-cis,13-trans-prosta-                                         5-cis,13-trans-                                                                              dienoates                                                      prostadienoate                                                                (Example 1205)                                                        1271    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-8-                                                                            8-iso-5-cis,13-trans-                                          iso-5-cis,13-  prostadienoates                                                trans-prostadien-                                                             oate (Example                                                                 1205)                                                                 1272    ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,-                         9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-                                                                              5-cis,13-cis-prostadi-                                         5-cis,13-cis-  enoates                                                        prostadienoate                                                                (Example 1205)                                                        1273    ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-                                                                              8-iso-5-cis,13-cis-                                            8-iso-5-cis,13-                                                                              prostadienoates                                                cis-prostadien-                                                               oate (Example                                                                 1205)                                                                 ______________________________________                                    

EXAMPLE 1274-1299

In the manner of Example 93, the various cyclopentanones of Table 36,which follows, are converted to the correspnding 4-bromo derivatives.

                  TABLE 36                                                        ______________________________________                                                  Starting                                                            Ex-       Cyclopentenone                                                                             Product 4-Bromocyclo-                                  ample     of Example   pentenones                                             ______________________________________                                        1274      13           4-bromo-2-(6-carbeth-                                                         oxyhexyl)-cyclopent-2-                                                        en-1-one                                               1275      83           4-bromo-2-(6-carbo-                                                           methoxyhexyl)cyclopent-                                                       2-en-1-one                                             1276      15           4-bromo-2-(4-carbeth-                                                         oxybutyl)cyclopent-2-en-                                                      1-one                                                  1277      14           4-bromo-2-(3-carbethoxy-                                                      propyl)cyclopent-2-en-1-                                                      one                                                    1278       2           4-bromo-2-(4-carboxy-                                                         butyl)cyclopent-2-en-                                                         1-one                                                  1279       5           4-bromo-2-(3-carboxy-                                                         propyl)cyclopent-2-en-1-                                                      one                                                    1280      22           4-bromo-2-(8-carboxy-                                                         octyl)cyclopent-2-en-1-                                                       one                                                    1281      23           4-bromo-2-(8-carbethoxy-                                                      octyl)cyclopent-2-en-1                                                        one                                                    1282      30           4-bromo-2-(6-carboxy-                                                         octyl)cyclopent-2-en-1-                                                       one                                                    1283      31           4-bromo-2-(6-carbethoxy-                                                      octyl)cyclopent-2-en-1-                                                       one                                                    1284      92           4-bromo-2-(6-carboxy-                                                         5,5-dimethylhexyl)cyclo-                                                      pent-2-en-1-one                                        1285      41           4-bromo-2-(6-carbethoxy-                                                      5,5-dimethylhexyl)cyclo-                                                      pent-2-en-1-one                                        1286      45           4-bromo-2-(6-carboxy-5-                                                       oxahexyl)cyclopent-2-                                                         en-1-one                                               1287      46           4-bromo-2-(6-carbethoxy-                                                      5-oxahexyl)cyclopent-2-                                                       en-1-one                                               1288      69           4-bromo--2-(6-carboxy-6-                                                      fluorohexyl)cyclopent-                                                        2-en-1-one                                             1289      70           4-bromo-2-(6-carbethoxy-                                                      6-fluorohexyl)cyclopent-                                                      2-en-1-one                                             1290      52           4-bromo-2-(5-carboxy-                                                         pentyl)cyclopent-2-en-1-                                                      one                                                    1291      53           4-bromo-2-(5-carbethoxy-                                                      pentyl)cyclopent-2-en-                                                        1-one                                                  1292      73           4-bromo-2-(7-carboxy-                                                         heptyl)cyclopent-2-en-1-                                                      one                                                    1293      74           4-bromo-2-(7-carbethoxy-                                                      heptyl)cyclopent-2-en-1-                                                      one                                                    1294      78           4-bromo-2-(6-carboxy-6-                                                       phenylhexyl)cyclopent-2-                                                      en-1-one                                               1295      79           4-bromo-2-(6-carbethoxy-                                                      6-phenylhexyl)cyclopent-                                                      2-en-1-one                                             1296      81           4-bromo-2-(6-carbo-n-                                                         butoxyhexyl)cyclopent-                                                        2-en-1-one                                             1297      82           4-bromo-2-(6-carbo-iso-                                                       propoxyhexyl)-cyclo-                                                          pent-2-en-1-one                                        1298      84           4-bromo-2-(6-carbo-n-                                                         decycloxyhexyl)cyclopent-                                                     2-en-1-one                                             1299      98           4-bromo-2-(6-carboxy-                                                         heptyl)-cyclopent-2-en-                                                       1-one                                                  ______________________________________                                    

EXAMPLE 1300 Preparation of4-hydroxy-2-(8-carboxyoctyl)cyclopent-2-en-1-one

To a stirred solution of 57.2 g. of crude4-bromo-2-(8-carboxyoctyl)cyclopent-2-en-1-one (Example 1280) in 500 ml.of acetone and 325 ml. of water at 3° C. is added 44.1 g. (0.226 moles)of silver fluoborate during a 15 minute period. The mixture is stirredat 0°-3° C. for 2 hours and filtered. The filtrate is diluted withwater, saturated with solid sodium chloride, and extracted with ether.The extract is washed with saturated sodium chloride solution, driedover magnesium sulfate, and concentrated. Partition chromatography ofthe residue on Celite gives white crystals, m.p. 58°-66° C.,μ_(max).^(MeOH) =223 mμ (7800); νmax (KBr)=3340 (hydroxyl groups), 1705(carbonyl groups), and 1625 cm⁻¹ (olefin group).

EXAMPLE 1301 Preparation of4-acetoxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

A mixture of 51.6 g. (0.137 moles) of crude4-bromo-2-(S-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1274), 27 g.(0.162 moles) of silver acetate, and 200 ml. of glacial acetic acid isstirred at reflux for 4.5 hours. The mixture is cooled, and solids areremoved by filtration. The filtrate is concentrated and extracted withhot hexane. The extract is washed with saturated sodium bicarbonatesolution and saturated sodium chloride solution, dried over mangesiumsulfate, and concentrated to give an oil. The crude product is distilledat reduced pressure to give a liquid, b.p. 152°-163° C. (0.01 mm);λ_(max).^(MeOh) =223 mm (10700);νmax.=1745 (ester carbonyl groups), 1725(ketone carbonyl groups), and 1235 cm⁻¹ (acetoxy group).

EXAMPLES 1302-1326

By the procedure of Example 94 the various 4-bromo-cyclopentenones ofthe following Table 37 are solvolyzed in acetone-water in the presenceof silver fluoborate to provide the produce 4-hydroxycyclopentenones ofthe Table.

                  Table 37                                                        ______________________________________                                                Starting 4-bromo-                                                                            Product                                                Ex-     cyclopentenones                                                                              4-Hydroxycyclopent-2-                                  ample   of Example     en-1-ones                                              ______________________________________                                        1302    1274           4-hydroxy-2-(6-carb-                                                          ethoxyhexyl)cyclopent-                                                        2-en-1-one                                             1303    1275           4-hydroxy-2-(6-carbo-                                                         methoxyhexyl)cyclopent-                                                       2-en-1-one                                             1304    1276           4-hydroxy-2-(4-carb-                                                          ethoxybutyl)cyclopent-                                                        2-en-1-one                                             1305    1277           4-hydroxy-2-(3-carb-                                                          ethoxypropyl)cyclopent-                                                       2-en-1-one                                             1306    1278           4-hydroxy-2-(4-carboxy-                                                       butyl)cyclopent-2-en-                                                         1-one                                                  1307    1279           4-hydroxy-2-(3-carboxy-                                                       propyl)cyclopent-2-en-                                                        1-one                                                  1308    1281           4-hydroxy-2-(8-carb-                                                          ethoxyoctyl)cyclopent-                                                        2-en-1-one                                             1309    1282           4-hydroxy-2-(6-carboxy-                                                       octyl)cyclopent-2-en-                                                         1-one                                                  1310    1283           4-hydroxy-2-(6-carb-                                                          ethoxyoctyl)cyclopent-                                                        2-en-1-one                                             1311    1284           4-hydroxy-2-(6-carboxy-                                                       5,5-dimethylhexyl)-                                                           cyclopent-2-en-1-one                                   1312    1285           4-hydroxy-2-(6-carb-                                                          ethoxy-5,5-dimethyl-                                                          hexyl)cyclopent-2-en-                                                         1-one                                                  1313    1286           4-hydroxy-2-(6-carboxy-                                                       5-oxahexyl)cyclopent-                                                         2-en-1-one                                             1314    1287           4-hydroxy-2-(6-carb-                                                          ethoxy-5-oxahexyl)-                                                           cyclopent-2-en-1-one                                   1315    1288           4-hydroxy-2-(6-carboxy-                                                       6-fluorohexyl)cyclo-                                                          pent-2-en-1-one                                        1316    1289           4-hydroxy-2-(6-carb-                                                          ethoxy-6-fluorohexyl)-                                                        cyclopent-2-en-1-one                                   1317    1290           4-hydroxy-2-(5-carboxy-                                                       pentyl)cyclopent-2-en-                                                        1-one                                                  1318    1291           4-hydroxy-2-(5-carb-                                                          ethoxypentyl)cyclo-                                                           pent-2-en-1-one                                        1319    1292           4-hydroxy-2-(7-carboxy-                                                       heptyl)cyclopent-2-en-                                                        1-one                                                  1320    1293           4-hydroxy-2-(7-carb-                                                          ethoxyheptyl)cyclopent-                                                       2-en-1-one                                             1321    1294           4-hydroxy-2-(6-carboxy-                                                       6-phenylhexyl)cyclo-                                                          pent-2-en-1-one                                        1322    1295           4-hydroxy-2-(6-carb-                                                          ethoxy-6-phenylhexyl)-                                                        cyclopent-2-en-1-one                                   1323    1296           4-hydroxy-2-(6-carbo-                                                         n-butoxyhexyl)cyclo-                                                          pent-2-en-1-one                                        1324    1297           4-hydroxy-2-(6-carbo-                                                         isopropoxyhexyl)cyclo-                                                        pent-2-en-1-one                                        1325    1298           4-hydroxy-2-(6-carbo-                                                         n-decycloxyhexyl)cyclo-                                                       pent-2-en-1-one                                        1326    1299           4-hydroxy-2-(6-carboxy-                                                       heptyl)cyclopent-2-en-                                                        1-one                                                  ______________________________________                                    

EXAMPLES 1327-1357

By the procedure of Example 95, the various 4-hydroxy-cyclopentenones ofTable 38, which follows, are converted to the tetrahydropyranyl4-tetrahydropyranyloxycyclopentenone esters of the table.

                  Table 38                                                        ______________________________________                                                               Product Tetrahydropyran-                                       Starting 4-hy- 2'-yl 4-tetrahydropy-                                  Ex-     droxycyclopenten-                                                                            ran-2'-yl-oxycyclopent-                                ample   one of Example 2-en-1-ones                                            ______________________________________                                        1327    1306           4-tetrahydropyra-2'-                                                          yloxy-2-(4-carbotetra-                                                        hydropyran-2'-yloxy-                                                          butyl)cyclopent-2-en-1-                                                       one                                                    1328    1307           4-tetrahydropyra-2'-                                                          yloxy-2-(3-carbotetra-                                                        hydropyran-2'-yloxy-                                                          propyl)cyclopent-2-en-                                                        1-one                                                  1329    1300           4-tetrahydropyra-2'-                                                          yloxy-2-(8-carbotetra-                                                        hydropyran-2'-yloxy-                                                          octyl)cyclopent-2-en-1-                                                       one                                                    1330    1309           4-tetrahydropyra-2'-                                                          yloxy-2-(6-carbotetra-                                                        hydropyra-2'-yloxy-                                                           octyl)cyclopent-2-en-1-                                                       one                                                    1331    1311           4-tetrahydropyra-2'-                                                          yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-                                                          5,5-dimethylhexyl)-                                                           cyclopent-2-en-1-one                                   1332    1313           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyra-2'--yloxy-5-                                                        oxahexyl)cyclopent-2-                                                         en-1-one                                               1333    1315           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-6-                                                        fluorohexyl)cyclopent-                                                        2-en-1-one                                             1334    1317           4-tetrahydropyran-2'-                                                         yloxy-2-(5-carbotetra-                                                        hydropyra-2'-yloxy-                                                           pentyl)cyclopent-2-en-1-                                                      one                                                    1335    1319           4-tetrahydropyran-2'-                                                         yloxy-2-(7-carbotetra-                                                        hydroxypyran-2'-yloxyhep-                                                     tyl)cyclopent-2-en-1-                                                         one                                                    1336    1321           4-tetrahydropyran-2'-                                                         yloxy-2-(96-carbotetra-                                                       hydropyra-2'-yloxy-6-                                                         phenylhexyl)cyclopent-                                                        2-en-1-one                                             1337    1326           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyra-2'-yloxy-                                                           heptyl)cyclopent-2-en-                                                        1-one                                                  ______________________________________                                    

EXAMPLE 1338 Preparation of4-tetrahydropyranyloxy-2-(6-carbethoxyhexyl)-cyclopent-2-en-1-one

To a stirred solution of 674 mg. (2.64 mmoles) of4-hydroxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1302) and2.22 g. (26.4 mmoles) of dihydropyran in 2.6 ml. of methylene chlorideis added 5.0 mg. (0.026 mmoles) of p-toluenesulfonic acid monohydrate.After stirring for 20 minutes at room temperature the solution isdiluted with ether and poured into saturated sodium chloride solutioncontaining a little sodium bicarbonate. The organic phase is separatedand washed with saturated sodium chloride solution. The extract is driedover magnesium sulfate, and volatile matter is evaporated at reducedpressure to give an oil, λ_(max).^(MeOH) =224 mμ(7950); max. = 1735(ester carbonyl group), 1710 (ketone carbonyl group), and 1030 cm⁻¹(tetrahydropyran-yloxy group).

EXAMPLE 1339-1352

In the manner of Example 1338 the alkyl 4-hydroxy-cyclopentenone estersof Table 39, which follows, are converted to the corresponding4-tetrahydropyranyloxy alkyl esters of the table.

                  TABLE 39                                                        ______________________________________                                                Starting 4-                                                                   hydroxycyclo-  4-tetrahydropyran-                                     Ex-     pentenone Esters                                                                             2'yloxycyclopent-                                      ample   of Example     2-en-1-one esters                                      ______________________________________                                        1339    1303           4-tetrahydropyran-2'-                                                         ylox-2-(6-carbomethoxy-                                                       hexyl)cyclopent-2-en-1-                                                       one                                                    1340    1304           4-tetrahydropyran-2'-                                                         yloxy-2-(4-carbethoxy-                                                        butyl)cyclopent-2-en-1-                                                       one                                                    1341    1305           4-tetrahydropyran-2'-                                                         yloxy-2-(3-carbethoxy-                                                        propyl)cyclopent-2-en-1-                                                      one                                                    1342    1308           4-tetrahydropran-2'-                                                          yloxy-2-(8-carbethoxy-                                                        octyl)cyclopent-2-en-1-                                                       one                                                    1343    1310           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-                                                        octyl)cyclopent-2-en-1-                                                       one                                                    1344    1312           4-tetrahydropran-2'-                                                          yloxy-2-(6-carbethoxy-5-                                                      5-dimethylhexyl)cyclo-                                                        pent-2-en-1-one                                        1345    1314           4-tetrahydropran-2'-                                                          yloxy-2-(6-carbethoxy-5-                                                      oxahexyl)cyclopent-2-en-                                                      1-one                                                  1346    1316           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-6-                                                      fluorohexyl)cyclopent-                                                        2-en-1-one                                             1347    1318           4-tetrahydropyran-2'-                                                         yloxy-2-(5-carbethoxy-                                                        pentyl)cyclopent-2-en-                                                        1-one                                                  1348    1320           4-tetrahydropran-2'-                                                          yloxy-2-(7-carbethoxy-                                                        heptyl)cyclopent-2-en-1-                                                      one                                                    1349    1322           4-tetrahydropran-2'-                                                          yloxy-2-(6-carbethoxy-6-                                                      phenylhexyl)cyclopent-2-                                                      en-1-one                                               1350    1323           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-n-                                                           butoxyhexyl)cyclopent-2-                                                      en-1-one                                               1351    1324           4-tetrahydropran-2'-                                                          yloxy-2-(6-carbo-iso-                                                         propoxyhexyl)cyclopent-                                                       2-en-1-one                                             1352    1325           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-n-dec-                                                       yloxyhexyl)cyclopent-2-                                                       en-1-one                                               ______________________________________                                    

EXAMPLE 1353 Preparation of 8β-methyl-prostaglandinE₁,8α-methyl-8-isoprostaglandinE₁,8β-methyl-9-oxo-11α,15-dihydroxy-13-cisprostenoic acid, and8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-prostenoic acid

The Grignard reagent, prepared as described in Example 1187 from 1.54 g.of magnesium, 22.5 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene(Example 728), and 30 ml. of tetrahydrofuran, is added to an ice cooledsolution of 17.75 g. of11-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxyhexyl)-2-cyclopentenone(Example 95) and 1.25 g. of copper (I) iodide-tri-n-butylphosphinecomplex in 30 ml. of tetrahydrofuran over 15 minutes under an inertatmosphere. The mixture is stirred with cooling for 0.5 hour. To themixture is then added 100 g. of methyl iodide, the cooling bath is thenremoved and the mixture is stirred at ambient temperatures for 48 hours.The mixture is then poured into ice cold saturated ammonium chloridesolution and the layers are separated. The aqueous phase is washed withether and combined organic phase and washings are washed with saturatedbrine, and evaporated in vacuo. The residue is heated to 45° C. for 5hours with 840 ml. of 4:2:1 tetrahydrofuranacetic acid-water under aninert atmosphere and is then evaporated to dryness in vacuo. The residueis chromatographed upon Silic AR CC-4.sup.® using a benzene-ethylacetate gradient as eluent to yield the title compounds as a mixture of8β-methyl-prostaglandin E₁ ; and 8α-methyl-8-iso-prostaglandin E₁ and amixture of 8β-methyl-9-oxo-11α,15-dihydroxy-13-cisprostenoic acid and8α-methyl-9-oxo-11α,15-dihydroxy 8-iso-cis-8αisomers; resolution of themixtures is then accomplished by a combination of partitionchromatography and thin-layer chromotography.

EXAMPLES 1354-1386

Treatment of the blocked 4-oxycyclopent-2-en-1-ones listed in Table 40below by the procedure described in Example 1353 with the Grignardreagents, prepared by the procedure described in Example 1187 from thelisted 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyliodide furnishes the product 8α- and 8β-methyl prostenoates of thetable. The products of Examples 1354-1378 inclusive are initiallyobtained as the corresponding15-O-triphenyl-methyl-11-O-tetrahydropyranyl tetrahydropyranyl esters.These blocking groups are then cleaved by the procedure described inExample 1353 by treatment at 45° C. for five hours with 4:2:1tetrahydrofuran:acetic acid:water. The alkyl esters products of Examples1379-1385 inclusive are obtained initially as the corresponding15-O-triphenyl-methyl-11-O-tetrahydropyranyl derivatives. These 11- and15-hydroxy blocking groups are then cleaved by the deblocking proceduredescribed in Example 1353. The products of Example 1386 are initiallyobtained as the corresponding 15-O-triphenylmethyl derivatives, whichare cleaved hydrolytically to the listed free 15 -ols by the processdescribed in Example 1353.

                                      TABLE 40                                    __________________________________________________________________________        Starting blocked                                                                       Starting 1-bromo-                                                    4-oxycylopent-                                                                         3-triphenylmethoxy-                                              Ex- 2-en-1-one of                                                                          1-trans-alkene of                                                ample                                                                             Example  Example   Product 8-methylprostenoic acid                        __________________________________________________________________________    1354                                                                               95      1175      8β-methyl-9-oxo-11α,15-dihydroxy-16,16-                            N                                                                             dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           O                                                                             dimethyl-8-iso-13-trans-prostenoic acid                                       8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           1                                                                             dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           `                                                                             dimethyl-8-iso-13-cis-prostenoic acid                  1355                                                                               95      1178      8β-methyl-9-oxo-11α,15-dihydroxy,17,17-                            Z                                                                             dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-17,17-                           2                                                                             dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-17,17-                            `                                                                             dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-17,17-                           Z                                                                             dimethyl-8-iso-13-cis-prostenoic acid                  1356                                                                               95      1182      8β-methyl-9-oxo-11α,15-dihydroxy-13-tran                           s,                                                                            17-cis-prostadienoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           13-                                                                           trans,17-cis-prostadienoic acid                                               8β-methyl-9-oxo-11α,15-dihydroxy-13-cis,                           Z                                                                             17-cis-prostadienoic acid                                                     8α-methyl-9-oxo-11αc15-dihydroxy-8-iso-                           13-                                                                           cis,17-cis-prostadienoic acid                          1357                                                                               95      1185      8β-methyl-9-oxo-11α,15-dihydroxy-20-ethy                           l-                                                                            13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-20-eth                           yl-                                                                           8-iso-13-trans-prostenoic acid                                                8β-methyl-9-oxo-11α,15-dihydroxy-20-ethy                           l-                                                                            13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-20-eth                           yl-                                                                           8-iso-13-cis-prostenoic acid                           1358                                                                              1327      728      8β-methyl-9-oxo-11α,15-dihydroxy-6,7-din                           or-                                                                           13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-6,7-di                           nor-                                                                          8-iso-13-trans-prostenoic acid                                                8β-methyl-9-oxo-11α,15-dihydroxy-6,7-din                           or-                                                                           13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-6,7-di                           nor-                                                                          8-iso-13-cis-prostenoic acid                           1359                                                                              1328     1186      8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-t                           ri-                                                                           nor-20-methyl-13-trans-prostenoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7-                           tri-                                                                          nor-20-methyl-8-iso-13-trans-prostenoic acid                                  8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-t                           ri-                                                                           nor-20-methyl-13-cis-prostenoic acid                                          8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7-                           tri-                                                                          nor-20-methyl-8-iso-13-cis-prostenoic acid             1360                                                                              1329      728      8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-b                           is-                                                                           homo-13-trans-prostenoic acid                                                 9α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-                           bis-                                                                          homo-8-iso-13-trans-prostenoic acid                                           8β-methyl-9-oxo-11α,15-dihydroxy-7a.7b-b                           is-                                                                           homo-13-cis-prostenoic acid                                                   8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-                           bis-                                                                          home-8-iso-13-cis-prostenoic acid                      1361                                                                              1330      728      8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl                           -13-                                                                          trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-2-ethy                           l-8-                                                                          iso-13-trans-prostenoic acid                                                  8α-methyl-9-oxo-11α,15-dihydroxy-2-ethy                           l-13-                                                                         cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-2-ethy                           l-8-                                                                          iso-13-cis-prostenoic acid                             1362                                                                              1331     1186      8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20-                           tri-                                                                          methyl-13-trans-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3,3,20                           -tri-                                                                         methyl-8-iso-13-trans-prostenoic acid                                         8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20-                           tri-                                                                          methyl-13-cis-prostenoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-3,3,20                           -tri-                                                                         methyl-8-iso-13-cis-prostenoic acid                    1363                                                                              1332      728      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-iso-                                                                        13-trans-prostenoic acid                                                      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-                                                                            iso-13-cis-prostenoic acid                             1364                                                                              1332     1175      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           6,16-                                                                         dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           16,16-                                                                        dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-8-oxo-11α,15-dihydroxy-3-oxa-1                           6,16-                                                                         dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           16,16-                                                                        dimethyl-8-iso-13-cis-prostenoic acid                  1365                                                                              1332     1182      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            trans,17-cis-prostadienoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-iso-                                                                        13-trans,17-cis-prostadienoic acid                                            8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            ics,17-cis-prostadienoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-iso-                                                                        13-cis,17-cis-prostadienoic acid                       1366                                                                              1332     1185      8β-methyl-9-oxo-11-60 ,15-dihydroxy-3-oxa-20-                            f                                                                             ethyl-13-trans-prostenoic acid                                                8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           20-                                                                           ethyl-8-iso-13-trans-prostenoic acid                                          8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-2                           0-                                                                            ethyl-13-cis-prostenoic acid                                                  8α-methyl-9-oxo-11 60 ,15-dihydroxy-3-oxa-20-                           r                                                                             ethyl-8-iso-13-cis-prostenoic acid                     1367                                                                              1333     1178      8β-methyl-9-oxo-11α,15-dihydroxy-2-fluor                           o-                                                                            17,17-dimethyl-13-trans-prostenoic acid                                       8α-methyl-9-oxo-11α,15-dihydroxy-2-fluo                           ro-                                                                           17,17-dimethyl-8-iso-13-trans-prostenoic acid                                 8β-methyl-9-oxo-11α,15-dihydroxy-2-fluor                           o-                                                                            17,17-dimethyl-13-cis-prostenoic acid                                         8α-methyl-9-oxo-11α,15-dihydroxy-2-fluo                           ro-                                                                           17,17-dimethyl-8-iso-13-cis-prostenoic acid            1368                                                                              1334      728      8β-methyl-9-oxo-11α,15-dihydroxy-7-nor-1                           3-                                                                            trans-prostenoic acid                                                         8α-methyl-9-oxo-11α-dihydroxy-7-nor-8-                            l                                                                             iso-13-trans-prostenoic acid                                                  8β-methyl-9-oxo-11-60 ,15-dihydroxy-7-nor-13-                            .                                                                             cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-7-nor-                           8-                                                                            iso-13-cis-prostenoic acid                             1369                                                                              1335     1175      8β-methyl-9-oxo-11α,15-dihydroxy-7a-homo                           -                                                                             16,16-dimethyl-13-trans-prostenoic acid                                       8α-methyl-9-oxo-11α,15-dihydroxy-7a-hom                           o-16,16-                                                                      dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-7a-homo                           -                                                                             16,16-dimethyl-13-cis-prostenoic acid                                         8α-methyl-9-oxo-11α,15-dihydroxy-7a-hom                           o-                                                                            16,16-dimethyl-8-iso-13-cis-prostenoic acid            1370                                                                              1336      728      8β-methyl-9-oxo-11α,15-dihydroxy-2-pheny                           l-                                                                            13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-2-phen                           yl-                                                                           8-iso-13-trans-prostenoic acid                                                8β-methyl-9-oxo-11α,15-dihydroxy-2-pheny                           l-                                                                            13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-2-phen                           yl-                                                                           8-iso-13-cis-prostenoic acid                           1371                                                                              1337     1162      8β-methyl-9-oxo-11α,15-dihydroxy-2-methy                           l-                                                                            13-trans,17-cis-prostadienoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-2-meth                           yl-                                                                           8-iso-13-trans,17-cis-prostadienoic acid                                      8β-methyl-9-oxo-11α,15-dihydroxy-2-methy                           l-                                                                            13-cis,17-cis-prostadienoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-2-meth                           yl-                                                                           8-iso-13-cis,17-cis-prostadenoic acid                  1372                                                                              1121      728      8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,1                           3-                                                                            trans-prostadienoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           5-                                                                            cis,13-trans-prostadienoic acid                                               8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,1                           3-                                                                            cis-prostadienoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           5-                                                                            cis,13-cis-prostadienoic acid                          1373                                                                              1121     1182      8β-methyl-9-oxo-11α,15-hydroxy-5-cis,13-                           Z                                                                             trans,17-cis-prostatrienoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           5-                                                                            cis,13-trans,17-cis-prostatrienoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,                            3                                                                             13-cis,17-cis-prostatrienoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           -                                                                             5-cis,13-cis,17-cis-prostatrienoic acid                1374                                                                              1121     1175      8β-methyl-9-oxo-11α,15-dihydroxy-16,16-d                           i-                                                                            methyl-5-cis,13-trans-prostadienoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           di-                                                                           methyl-8-iso-5-cis,13-trans-prostadienoic acid                                8β-methyl-9-oxo-11α,15-dihydroxy-16,16-d                           i-                                                                            methyl-5-cis,13-cis-prostadienoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           di-                                                                           methyl-8-iso-5-cis,13-cis-prostadienoic acid           1375                                                                              1122     186       8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-2                           0-                                                                            methyl-5-cis,13-trans-prostadienoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-4-nor-                           20-                                                                           methyl-8-iso-5-cis,13-trans-prostadienoic acid                                8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-2                           0-                                                                            methyl-5-cis,13-cis-prostadienoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-4-nor-                           20-                                                    methyl-8-iso-5-cis,13-cis-prostadienoic acid                                  1376                                                                              1123     1178      8β-methyl-9-oxo-11α,15-dihydroxy-4a-homo                           -17,                                                                          17-dimethyl-5-cis,13-trans-prostadienoic acid                                 8α-methyl-9-oxo-11α,15-dihydroxy-4a-hom                           o-17,                                                                         17-dimethyl-8-iso-5-cis,13-cis-prostadienoic                                  acid                                                                          8β-methyl-9-oxo-11α,15-dihydroxy-4a-homo                           -17,                                                                          17-dimethyl-5-cis,13-cis-prostadienoic acid                                   8α-methyl-9-oxo-11α,15-dihydroxy-4a-hom                           o-17,                                                                         17-dimethyl-8-iso-5-cis,13-cis-prostadienoic                                  acid                                                   1377                                                                              1124     1185      8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-b                           is-                                                                           homo-20-ethyl-5-cis,13-trans-prostadienoic                                    acid                                                                          8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-20-ethyl-8-iso-5-cis,13-trans-prost-                                     dienoic acid                                                                  8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-b                           is-                                                                           homo-20-ethyl-5-cis,13-cis-prostadienoic acid                                 8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-20-ethyl-8-iso-5-cis,13-cis-prosta-                                      dienoic acid                                           1378                                                                              1124     1182      8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-b                           is-                                                                           homo-5-cis,13-trans,17-cis-prostatrienoic                                     acid                                                                          8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-8-iso-5-cis,13-trans,17-cis-prosta-                                      trienoic acid                                                                 8β-methyl-9-oxo-11α,15-hydroxy-4a,4b-bis                           -                                                                             homo-5-cis,13-cis,17-cis-prostatrienoic acid                                  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-8-iso-5-cis,13-cis-17-cis-prostatrienoic                                 acid                                                   1379                                                                              1339     1186      Methyl 8β-methyl-9-oxo-11α,15-dihydroxy-                           20-                                                                           methyl-13-trans-prostenoate                                                   Methyl 8α-methyl-9-oxo-11α,15-dihydroxy                           -20-                                                                          methyl-8-iso-13-trans-prostenoate                                             Methyl 8β-methyl-9-ox-11α                                          ,15-dihydroxy-20-                                                             methyl-13-cis-prostenoate                                                     Methyl 8α-methyl-9-oxo-11α,15-dihydroxy                           -20-                                                                          methyl-8-iso-13-cis-prostenoate                        1380                                                                              1342     1182      Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7                           a,7b-                                                                         bishomo-13-trans,17-cis-prostadienoate                                        Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           7a,7b-                                                                        bishomo-8-iso-13-trans,17-cis-prostadienoate                                  Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7                           a,7b-                                                                         bishomo-13-cis,17-cis-prostadienoate                                          Ethyl 8α-methyl-9-oxo-11-α,15-dihydroxy                           -7a,7b-                                                                       bishomo-8-iso-13-cis,17-cis-prostadienoate             1381                                                                              1343     1175      Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-2                           -                                                                             ethyl-16,16-dimethyl-13-trans-prostenoate                                     Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           2-                                                                            ethyl-16-16-dimethyl-8-iso-13-trans-                                          prostenoate                                                                   Ethyl 9β-methyl-9-oxo-11α,15-dihydroxy-2                           -                                                                             ethyl-16,16-dimethyl-13-cis-prostenoate                                       Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           2-                                                                            ethyl-16,16-dimethyl-8-iso-13-cis-prostenoate          1382                                                                              1344     1178      Ethyl 8β-,ethyl-9-oxo-11α,15-dihydroxy-3                           ,3-                                                                           17,17-tetramethyl-13-trans-prostenoate                                        Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3,3-                                                                          17,17-tetramethyl-8-iso-13-trans-prostenoate                                  Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3                           ,3-                                                                           17,17-tetramethyl-13-cis-prostenoate                                          Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3,3-                                                                          17,17-tetramethyl-8-iso-13-cis-prostenoate             1383                                                                              1345     1178      Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3                           -oxa-                                                                         17,17-dimethyl-13-trans-prostenoate                                           Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3-oxa-                                                                        17,17-dimethyl-8-iso-13-trans-prostenoate                                     Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3                           -oxa-                                                                         17,17-dimethyl-13-cis-prostenoate                                             Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3-oxa-                                                                        17,17-dimethyl-8-iso-13-cis-prostenoate                1384                                                                              1350      728      Butyl 8β-methyl-9-oxo-11α,15-dihydroxy-1                           3-                                                                            trans-prostenoate                                                             Butyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           8-iso-                                                                        13-trans-prostenoate                                                          Butyl 8β-methyl-9-oxo-11α,15-dihydroxy-1                           3-                                                                            cis-prostenoate                                                               Butyl 8α-methyl-9-oxo-11α,15-hydroxy-8-                           iso-                                                                          13-cis-prostenoate                                     1385                                                                              1352     1182      Decyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            .                                                                             13-trans,17-cis-prostadienoate                                                Decyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           8-iso-                                                                        13-trans,17-cis-prostadienoate                                                Decyl 8β-methyl-9-oxo-11αc15-dihydroxy-1                           3-                                                                            cis-17-cis-prostadienoate                                                     Decyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           8-iso-                                                                        13-cis,17-cis-prostadienoate                           1386                                                                              1301      728      Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hyd                           roxy-                                                                         13-trans-prostenoate                                                          Ethyl 8α-methyl-9-oxo-11α-acetoxy-15-hy                           droxy-                                                                        8-iso-13-trans-prostenoate                                                    Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hyd                           oxy-                                                                          13-cis-prostenoate                                                            Ethyl 8α-methyl-9-oxo-11α-acetoxy-15-hy                           droxy-                                                                        8-iso-13-cis-prostenoate                               __________________________________________________________________________

EXAMPLE 1387 Preparation of 8β-methyl-prostaglandin A₁

A mixture of 0.30 g. of 8β-methyl-prostaglandin E₁ (Example 1353) and 10ml. of 1:9 aqueous acetic acid is heated to 65° C. for 18 hours under aninert atmosphere. The solvent is removed in vacuo and the residue ispurified upon Silic AR-CC-4.sup.® using a benzene-ethylacetate gradientto yield the title compound.

EXAMPLES 1388-1522

Treatment of the designated 8-methyl-9-oxo-11-hydroxy-prostenoic acidderivatives of Table 41 below with 1:9 aqueous acid and purification allas described in Example 1387 gives the corresponding8-methyl-9-oxo-10,13-prostadienoic acids and esters of the table.

                  TABLE 41                                                        ______________________________________                                               Starting 9-oxo- Product 8-methyl-9-oxo-                                Exam-  11-hydroxy      10,13-prostadienoic                                    ple    derivative      acids or esters                                        ______________________________________                                        1388   8α-methyl-8-iso-                                                                        8α-methyl-8-iso-prosta-                                 prostaglandin   glandin A.sub.1                                               E.sub.1 (Example 1353)                                                 1389   8β-methyl-9-oxo-                                                                         8β-methyl-11α,15-dihy-                             11α,15-dihy-                                                                            droxy-10,13-cis-prosta-                                       droxy-13-cis-   dienoic acid                                                  prostenoic acid                                                               (Example 1353)                                                         1390   8α-methyl-9-oxo-                                                                        8α-11α,15-dihy-                                   11α,15-dihy-                                                                            droxy-8-iso-10,13-cis-                                        droxy-8-iso-13- prostadienoic acid                                            cis-prostenoic                                                                acid (Example                                                                 1353)                                                                  1391   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihy-                                                                            droxy-16,16-dimethyl                                          droxy-16,16-di- 10,13-trans-prostadie-                                        methyl-13-trans-                                                                              noic acid                                                     prostenoic acid                                                               (Example 1354)                                                         1392   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihy-                                                                            droxy-16,16-dimethyl                                          droxy-16,16-di- 8-iso-10,13-trans-pro-                                        methyl-18-iso-13-                                                                             stadienoic acid                                               trans-proste-                                                                 noic acid Exam-                                                               ple 1354)                                                              1393   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-16,16-dimethyl                                          xy-16,16-di-    10,13-cis-prostadienoic                                       methyl-13-cis-  acid                                                          prostenoic acid                                                               (Example 1354)                                                         1394   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    8-iso-10,13-cis-pro-                                          methyl-8-iso-13-                                                                              stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1354)                                                                  1395   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-17,17-dimethyl                                          xy-17,17-di-    10,13-trans-prostadie-                                        methyl 13-trans-                                                                              noic acid                                                     prostenoic acid                                                               (Example 1355)                                                         1396   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-17,17-dimethyl-                                         xy-17,17-di-    8-iso-10,13-trans-pro-                                        methyl-8-iso-13-                                                                              stadienoic acid                                               trans-prostenoic                                                              acid (Example                                                                 1355)                                                                  1397   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-17,17-dimethyl-                                         xy-17,17-di-    10,13-cis,prostadie-                                          methyl 13-cis-  noic acid                                                     prostenoic acid                                                               (Example 1355)                                                         1398   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-17,17-dimethyl-                                         xy-17,17-di-    8-iso-10,13-cis-pro-                                          methyl-8-iso-13-                                                                              stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1355)                                                                  1399   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-10,13-trans,17-                                         xy-13-trans,17- cis-prostatrienoic                                            cis-prostadi-   acid                                                          enoic acid                                                                    (Example 1356)                                                         1400   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-10,13-trans-                                      xy-8-iso-13-    17-cis-prostatrienoic                                         trans,17-cis-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1356)                                                                  1401   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-10,13-cis,17-cis- - xy-13-cis,17-cis- prostat                           rienoic acid                                                  prostadienoic                                                                 acid (Example                                                                 1356)                                                                  1402   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-10,13-cis,-                                       xy-8-iso-13-cis,-                                                                             17-cis-prostatrienoic                                         17-cis-prostadi-                                                                              acid                                                          enoic acid                                                                    (Example 1356) -1403                                                                          8β-methyl-9-oxo- 8β-methyl-9-oxo-15-hy-             11α,15-dihydro-                                                                         droxy-20-ethyl-10,13-                                         xy-20-ethyl-13- trans-prostadienoic                                           trans-proste-   acid                                                          noic acid (Exam-                                                              ple 1357)                                                              1404   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-20-ethyl-8-iso-                                         xy-20-ethyl-8-  10,13-trans-prostadi-                                         iso-13-trans-   enoic acid                                                    prostenoic acid                                                               (Example 1357)                                                         1405   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-20-ethyl-10,13-                                         xy-20-ethyl-13- cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 1357)                                                                  1406   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-20-ethyl-8-iso-                                         xy-20-ethyl-8-  10,13-cis-prostadie-                                          iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1357)                                                         1407   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-6,7-dinor-10,13-                                        xy-6,7-dinor-13-                                                                              trans-prostadienoic                                           trans-proste-   acid                                                          noic acid (Exam-                                                              ple 1358)                                                              1408   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-6,7-dinor-8-iso-                                        xy-6,7-dinor-8- 10,13-trans-prostadie-                                        iso-13-trans-   noic acid                                                     prostenoic acid                                                               (Example 1358)                                                         1409   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-6,7-dinor-10,13-                                        xy-6,7-dinor-13-                                                                              cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 (1358)                                                                 1410   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-6,7-dinor-8-iso-                                        xy-6,7-dinor-8- 10,13-cis-prostadie-                                          iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1358)                                                         1411   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl 10,13-trans-                                           20-methyl 13-   prostadienoic acid                                            trans-prostenoic                                                              acid (Example                                                                 1359)                                                                  1412   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl-8-iso-10,13-                                           20-methyl-8-iso-                                                                              trans-prostadienoic                                           13-trans-pro-   acid                                                          stenoic acid                                                                  (Example 1359)                                                         1413   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl 10,13-cis-pro-                                         20-methyl 13-   stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1359)                                                                  1414   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl-8-iso-10,13-                                           20-methyl-8-    cis-prostadienoic acid                                        iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1359)                                                         1415   8β-methyl-9-oxo-                                                                         8β -methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             10,13-trans-prostadie-                                        13-trans-pro-   noic acid                                                     stenoic acid                                                                  (Example 1360)                                                         1416   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             8-iso-10,13-trans-                                            8-iso-13-trans- prostadienoic acid                                            prostenoic acid                                                               (Example 1360)                                                         1417   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             10,13-cis-prostadie-                                          13-cis-proste-  noic acid                                                     noic acid (Exam-                                                              ple 1360)                                                              1418   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             8-iso-10,13-cis-pro-                                          8-iso-13-cis-   stadienoic acid                                               prostenoic acid                                                               (Example 1360)                                                         1419   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-ethyl-10,13-                                          xy-2-ethyl-13-  trans-prostadienoic                                           trans-proste-   acid                                                          noic acid (Exam-                                                              ple 1361)                                                              1420   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-ethyl-8-iso-                                          xy-2-ethyl-8-   10,13-trans-prostadi-                                         iso-13-trans-   enoic acid                                                    prostenoic acid                                                               (Example 1361)                                                         1421   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-ethyl-10,13-                                          xy-2-ethyl-13-  cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 1361)                                                                  1422   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-ethyl-8-iso-                                          xy-2-ethyl-8-   10,13-cis-prostadie-                                          iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1361)                                                         1423   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3,3,20-trimethyl-                                       xy-3,3,20-tri-  10,13-trans-prostadi-                                         methyl-13-trans-                                                                              enoic acid                                                    prostenoic acid                                                               (Example 1362)                                                         1424   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3,3,20-trimethyl-                                       xy-3,3,20-tri-  8-iso-10,13-trans-pro-                                        methyl-8-iso-13-                                                                              stadienoic acid                                               trans-proste-                                                                 noic acid                                                                     (Example 1362)                                                         1425   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3,3,20-trimethyl-                                       xy-3,3,20-tri-  10,13-cis-prostadie-                                          methyl-13-cis-  noic acid                                                     prostenoic acid                                                               (Example 1362)                                                         1426   8αmethyl-9-oxo-                                                                         8αmethyl9-oxo-15-hy-                                    11α,15-dihydro-                                                                         droxy-3,20-trimethyl- - xy-3,3,20-tri- 8-iso-10,13-                           cis-pro-                                                      methyl-8-iso-13-                                                                              stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1362)                                                                  1427   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-trans-                                      xy-3-oxa-13-    prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1363)                                                              1428   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-8-iso- 13,trans-prostadienoic                                        13-trans-proste-                                                                              acid                                                          noic acid (Exam-                                                              ple 1363)                                                              1429   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-cis-                                        xy-3-oxa-13-cis-                                                                              prostadienoic acid                                            Prostenoic acid                                                               (Example 1363)                                                         1430   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-3-iso- 13-cis-prostadienoic                                          13-cis-proste-  acid                                                          noic acid (Exam-                                                              ple 1363)                                                              1431   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-10,13-trans-pro-                                       dimethyl-13-    stadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1364)                                                              1432   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-8-iso-10,13-                                           dimethyl-8-iso- trans-prostadienoic                                           13-trans-proste-                                                                              acid                                                          noic acid (Exam-                                                              ple 1364)                                                              1433   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-10,13-cis-pro-                                         dimethyl-13-cis-                                                                              stadienoic acid                                               prostenoic acid                                                               (Example 1364)                                                         1434   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-8-iso-10,13-cis-                                       dimethyl-8-iso- prostadienoic acid                                            13-cis-proste-                                                                noic acid (Exam-                                                              ple 1364)                                                              1435   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-                                            xy-3-oxa-13-    trans,17-cis-prosta-                                          trans,17-cis-   trienoic acid                                                 prostadienoic                                                                 acid (Example                                                                 1365)                                                                  1436   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro                                                                          droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-8-iso- 13-trans,17-cis-pro-                                          13-trans,17-cis-                                                                              statrienoic acid                                              prostadienoic                                                                 acid (Example                                                                 1365)                                                                  1437   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-cis,-                                       xy-3-oxa-13-cis,-                                                                             17-cis-prostatrienoic                                         17-cis-prosta-  acid                                                          dienoic acid                                                                  (Example 1365)                                                         1438   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-8-iso- 13-cis,17-cis-prosta-                                         13-cis,17-cis-  trienoic acid                                                 prostadienoic                                                                 acid (Example                                                                 1365)                                                                  1439   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    10,13-trans-prostadie-                                        ethyl-13-trans- noic acid                                                     prostenoic acid                                                               (Example 1366)                                                         1440   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    8-iso-10,13-trans-                                            ethyl-8-iso-13- prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1366)                                                              1441   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   1α,15-dihydro-                                                                          droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    10,13-cis-prostadie-                                          ethyl-13-cis-   noic acid                                                     prostenoic acid                                                               (Example 1366)                                                         1442   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    8-iso-10,13-cis-pro-                                          ethyl-8-iso-13- stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1366)                                                                  1443   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-fluoro-17,7-                                          xy-2-fluoro-17,-                                                                              dimethyl-10,13-trans-                                         17-dimethyl-13- prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1367)                                                              1444   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-fluoro-17,17-                                         xy-2-fluoro-17,-                                                                              dimethyl-8-iso-10,13-                                         17-methyl-8-    trans-prostadienoic                                           iso-13-trans-   acid                                                          prostenoic acid                                                               (Example 1367)                                                         1445   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-fluoro-17,17-                                         xy-2-fluoro-17,-                                                                              dimethyl-10,13-cis-                                           17-dimethyl-13- prostadienoic acid                                            cis-prostenoic                                                                acid (Example                                                                 1367)                                                                  1446   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-fluoro-17,17-                                         xy-2-fluoro-17,-                                                                              dimethyl-8-iso-10,13-                                         17-dimethyl-8-  cis-prostadienoic acid                                        iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1367)                                                         1447   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7-nor-10,13-trans-                                      xy-7-nor-13-    prostadienoic acid                                            trans-prosta-                                                                 noic acid (Exam-                                                              ple 1368)                                                              1448   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydo-                                                                          droxy-7-nor-8-iso-10,-                                        xy-7-nor-8-iso- 13-trans-prostadienoic                                        13-trans-pro-   acid                                                          stenoic acid                                                                  (Example 1368)                                                         1449   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7-nor-10,13-cis-                                        xy-7-npor-13-cis-                                                                             prostadienoic acid                                            (Example 1368)                                                         1450   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7-nor-8-iso-10,-                                        xy 7-nor-8-iso- 13-cis-prostadienoic                                          13-cis-proste-  acid                                                          noic acid (Exam-                                                              Ple 1368)                                                              1451   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   1α,15-dihydro-                                                                          droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-10,13-trans-                                         16-dimethyl-13- prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1369)                                                              1452   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-8-iso-10,13-                                         16-dimethyl-8-  trans-prostadienoic                                           iso-13-trans-   acid                                                          prostenoic acid                                                               (Example 1369)                                                         1453   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-10,13-cis-                                           16-dimethyl-13- prostadienioic acid                                           cis-prostenoic                                                                acid (Example                                                                 1369)                                                                  1454   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-8-iso-10,13-                                         16-dimethyl-8-  cis-prostadienoic acid                                        iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1369)                                                         1455   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-phenyl-10,13-                                         xy-2-phenyl-13- trans-prostadienoic                                           trans-prostenoic                                                                              acid                                                          acid (Example                                                                 1370)                                                                  1456   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-phenyl-8-iso-                                         xy-2-phenyl-8-  10,13-trans-prostadi-                                         iso-13-trans-   enoic acid                                                    prostenoic acid                                                               (Example 1370)                                                         1457   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-phenyl-10,13-                                         xy-2-phenyl-13- cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 1370)                                                                  1458   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-phenyl-8-iso-                                         xy-2-phenyl-8-  10,13-cis-prostdie-                                           iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1370)                                                         1459   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-methyl-10,13-                                         xy-2-methyl-13- trans,17-cis-prosta-                                          trans-17-cis-   trienoic acid                                                 prostadienoic                                                                 acid (Example                                                                 1371)                                                                  1460   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-methyl-8-iso-                                         xy-2-methyl-8-  10,13-trans,17-cis-                                           iso-13-trans-   prostatrienoic acid                                           17-cis-prostadi-                                                              enoic acid                                                                    (Example 1371)                                                         1461   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-methyl-10,13-                                         xy-2-methyl-13- cis,17-cis-prostatri-                                         cis,17-cis-pro- enoic acid                                                    stadienoic acid                                                               (Example 1371)                                                         1462   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihdro-                                                                          droxy-2-methyl-8-iso-                                         xy-2-methyl-8-  10,13-cis,17-cis-pro-                                         iso-13-cis,17-  statrienoic acid                                              cis-prostadie-                                                                noic acid (Exam-                                                              ple 1371)                                                              1463   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,cis,10,13-trans-                                      xy-5,cis,13-    prostatrienoic acid                                           trans-prosta-                                                                 dienoic acid                                                                  (Example 1372)                                                         1464   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15--hy-                                 11α,15-dihydro-                                                                         droxy-8-iso-5,cis,10,-                                        xy-8-iso-5,cis,-                                                                              13-trans-prostatrienoic                                       13-trans-prosta-                                                                              acid                                                          dienoic acid                                                                  (Example 1372)                                                         1465   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,cis,10,13-cis-                                        xy-5,cis,13-cis-                                                                              prostatrienoic acid                                           prostadienoic                                                                 acid (Example                                                                 1372)                                                                  1466   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-5-hy-                                   11α,15-dihydro-                                                                         droxy-8-iso-5,cis,10,13-                                      xy-8-iso-5,cis,-                                                                              cis-prostatrienoic acid                                       13-cis-prostadi-                                                              enoic acid                                                                    (Example 1372)                                                         1467   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5-cis,10,13-                                            xy-5-cis,13-    trans,17-cis-prosta-                                          trans,17-cis-   tetraenoic acid                                               prostatrienoic                                                                acid (Example                                                                 1373)                                                                  1468   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-5-cis,10,-                                        xy-8-iso-5-cis,-                                                                              13-trans,17-cis-prosta-                                       13-trans,17-cis-                                                                              tetraeneoic acid                                              prostatrienoic                                                                acid (Example                                                                 1373)                                                                  1469   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5-cis,10,13-cis,-                                       xy-5-cis,13-cis,-                                                                             17-cis-prostatetrae-                                          17-cis-prosta-  neoic acid                                                    trienoic acid                                                                 (Example 1373)                                                         1470   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydo-                                                                          droxy-8-iso-5-cis,10,-                                        xy-8-iso-5-cis,-                                                                              13-cis,17-cis-prostate-                                       13-cis,17-cis-  traenoic acid                                                 prostatrienoic                                                                acid (Example                                                                 1373)                                                                  1471   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    5-cis,10,13-trans-pro-                                        methyl-5-cis,13-                                                                              statrienoic acid                                              trans-prostadi-                                                               enoic acid (Exam-                                                             ple 1374)                                                              1472   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    8-iso-5-cis,10,13-                                            methyl-8-iso-5- trans-prostatrienoic                                          cis,13-trans-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1374)                                                                  1473   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    5-cis,10,13-cis-pro-                                          methyl-5-cis,13-                                                                              statrienoic acid                                              cis-prostadie-                                                                noic acid (Exam-                                                              ple 1374)                                                              1474   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    8-iso-5-cis,10,13-cis-                                        methyl-8-iso-5- prostatrienoic acid                                           cis,13-cis-pro-                                                               stadienoic acid                                                               (Example 1374)                                                         1475   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    5-cis,10,13-trans-pro-                                        methyl-5-cis,-  statrienoic acid                                              13-trans-prosta-                                                              dienoic acid                                                                  (Example 1375)                                                         1476   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    8-iso-5-cis,10,13-                                            methyl-8-iso-   trans-prostatrienoic                                          5-cis,13-trans- acid                                                          prostadienoic                                                                 acid (Example                                                                 1375)                                                                  1477   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    5-cis,10,13-cis-pro-                                          methyl-5-cis,-  statrienoic acid                                              13-cis-prostadi-                                                              enoic acid                                                                    (Example 1375)                                                         1478   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihdyro-                                                                         droxy-4-nor-20-methyl-                                        11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    8-iso-5-cis,10,13-                                            methyl-8-iso-   cis-prostatrienoic                                            5-cis,13-cis-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1375)                                                                  1479   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-5-cis,10,13-                                           17-dimethyl-5-  trans-prostatrienoic                                          cis,13-trans-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1376)                                                                  1480   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-8-iso-5-cis,10-                                        17-dimethyl-8-  13-trans-prostatrienoic                                       iso-5-cis,13-   acid                                                          trans-prostadi-                                                               enoic acid (Exam-                                                             ple 1376)                                                              1481   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-5-cis,10,13-cis-                                       17-dimethyl-5-  prostatrienoic acid                                           cis,13-cis-pro-                                                               stadienoic acid                                                               (Example 1376)                                                         1482   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dohydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-8-iso-5-cis,10-                                        17-dimethyl-8-  13-cis-prostatrienoic                                         iso-5-cis,13-   acid                                                          cis-prostadie-                                                                noic acid (Exam-                                                              ;e 1376)                                                               1483   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bis-   20-ethyl-5-cis,10,13-                                         homo-20-ethyl-  trans-prostatrienoic                                          5-cis,13-trans- acid                                                          prostadienoic                                                                 acid (Example                                                                 1377)                                                                  1484   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bis-   20-ethyl-8-iso-5-cis,-                                        homo-20-ethyl-8-                                                                              10,13-trans-prostatrie-                                       iso-5-cis,13-   noic acid                                                     trans-prostadi-                                                               enoic acid                                                                    (Example 1377)                                                         1485   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bis-   20-ethyl-5-cis,10,13-                                         homo-20-ethyl-5-                                                                              cis-prostatrienoic                                            cis,13-cis-pro- acid                                                          stadienoic acid                                                               (Example 1377)                                                         1486   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bishomo-                                                                             20-ethyl-8-iso-5-cis,-                                        20-ethyl-8-iso- 10,13-cis-prostatrie-                                         5-cis,13-cis-   noic acid                                                     prostadienoic                                                                 acid (Example                                                                 1377)                                                                  1487   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bishomo-                                                                             5-cis,10,13-trans,17-                                         5-cis,13-trans,-                                                                              cis-prostatetraenoic                                          17-cis-prostatri-                                                                             acid                                                          enoic acid                                                                    (Example 1378)                                                         1488   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α-15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bishomo-                                                                             8-iso-5-cis,10,13-                                            8-iso-5-cis,13- trans,17-cis-prostate-                                        trans,17-cis-   traenoic acid                                                 prostatrienoic                                                                acid (Example                                                                 1378)                                                                  1489   8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-5-                                        xy-4a,4b-bishomo-                                                                             cis,10,13-cis-17-cis-                                         5-cis,13-cis-   prostatetraenoic acid                                         17-cis-prosta-  acid                                                          trienoic acid                                                                 (Example 1378)                                                         1490   8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydo-                                                                          droxy-4a,4b-bishomo-8-                                        xy-4a,4b-bishomo-                                                                             iso-5-cis,10,13-cis-                                          8-iso-5-cis,13- 17-cis-prostatetrae-                                          cis-17,cis-pro- noic acid                                                     statrienoic acid                                                              (Example 1378)                                                         1491   methyl 8β-methyl-                                                                        methyl 8β-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-methyl-                                                                            10,13-trans-prostadi-                                         13-trans-proste-                                                                              enoate                                                        noate (Example                                                                1379)                                                                  1492   methyl 8α-methyl-                                                                       methyl 8α-methyl-9-oxo-                                 9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-     8-iso-10,13-trans-pro-                                        methyl-8-iso-   stadienoate                                                   13-trans-pro-                                                                 stenoate (Exam-                                                               ple 1379)                                                              1493   methyl 8β-methyl-                                                                        methyl 8β-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-     10,13-cis-prostadie-                                          methyl-13-cis-  noate                                                         prostenoate                                                                   (Example 1379)                                                         1494   methyl 8α-methyl-                                                                       methyl 8α-methyl-9-oxo-                                 9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-     8-iso-10,13-cis-pro-                                          methyl-8-iso-   stadienoate                                                   13-cis-proste-                                                                noate (Example                                                                1379)                                                                  1495   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-7a,7b-bis-                                         hydroxy-7a,7b-  homo-10,13-trans,17-                                          bishomo-13-     cis-prostatrienoate                                           trans,17-cis-                                                                 prostadienoate                                                                (Example 1380)                                                         1496   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-7a,7b-bis-                                         hydroxy-7a,7b-  homo-8-iso-10,13-trans,-                                      bishomo-8-iso-  17-cis-prostatrienoate                                        13-trans,17-                                                                  cis-prostadie-                                                                noate (Example                                                                1380)                                                                  1497   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-                                                                           15-hydroxy-7a,7b-bis-                                         dihydroxy-7a,-  homo-10,13-cis,17-cis-                                        7b-bishomo-13-  prostatrienoate                                               cis,17-cis-pro-                                                               stadienoate                                                                   (Example 1380)                                                         1498   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-7a,7b-bis-                                         hydroxy-7a,7b-  homo-8-iso-10,13-cis,-                                        bishomo-8-iso-  17-cis-prostatrienoate                                        13-cis,17-cis-                                                                prostadienoate                                                                (Example 1380)                                                         1499   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-10,13-                                         16,16-dimethyl- trans-prostadienoate                                          13-trans-proste-                                                              noate (Example                                                                1381)                                                                  1500   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-8-iso-                                         16,16-dimethyl- 10,13-trans-prostadi-                                         8-iso-13-trans- enoate                                                        prostenoate                                                                   (Example 1381)                                                         1501   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-10,13-                                         16,16-dimethyl- cis-prostadienoate                                            13-cis-proste-                                                                noate (Example                                                                1381)                                                                  1502   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-8-iso-                                         16,16-dimethyl- 10,13-cis-prostadie-                                          8-iso-13-cis-   noate                                                         prostenoate                                                                   (Example 1381)                                                         1503   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy-3,3,17,-                                                                              tetramethyl-10,13-                                            17-tetramethyl- trans-prostadienoate                                          13-trans-proste-                                                              noate (Example                                                                1382)                                                                  1504   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy-3,3,17,-                                                                              tetramethyl-8-iso-10,-                                        17-tetramethyl-8-                                                                             13-trans-prostadienoate                                       iso-13-trans-pro-                                                             stenoate (Example                                                             1382)                                                                  1505   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy-3,3,17,-                                                                              tetramethyl-10,13-cis-                                        17-tetramethyl- prostadienoate                                                13-cis-proste-                                                                noate (Example                                                                1382)                                                                  1506   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy,3,3,17,-                                                                              tetramethyl-8-iso-10,-                                        17-tetramethyl- 13-cis-prostadienoate                                         8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1382)                                                         1507   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,-                                         hydroxy-3-oxa-  17-dimethyl-10,13-trans-                                      17,17-dimethyl- prostadienoate                                                13-trans-proste-                                                              noate (Example                                                                1383)                                                                  1508   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,17-                                       hydroxy-3-oxa-  dimethyl-8-iso-10,13-                                         17.17-dimethyl- trans-prostadienoate                                          8-iso-13-trans-                                                               prostenoate                                                                   (Example 1383)                                                         1509   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,17-                                       hydroxy-3-oxa-  dimethyl-10,13-cis-                                           17,17-dimethyl- prostadienoate                                                13-cis-proste-                                                                note (Example                                                                 1383)                                                                  1510   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,-                                         hydroxy-3-oxa-  17-dimethyl-8-iso-10,-                                        17,17-dimethyl- 13-cis-prostadienoate                                         8-iso-13-cis-                                                                 prostenoate                                                                   Example         1383)                                                  1511   butyl 8β-methyl-                                                                         butyl 8β-methyl-9-oxo-                                   9-oxo-11α9-oxo-11⊕,15-di-                                                           15-hydroxy-10,13-trans-                                       hydroxy-13-trans-                                                                             prostadieonate                                                prostenoate                                                                   (Example 1384)                                                         1512   butyl 8α,methyl-                                                                        butyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-8-iso-10,-                                         hydroxy-8-iso-13-                                                                             13-trans-prostadienoate                                       trans-prosteno-                                                               ate (Example                                                                  1384)                                                                  1513   butyl 8β-methyl-                                                                         butyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-13-cis-pro-                                        hydroxy-13-cis- stadienoate                                                   prostenoate                                                                   (Example 1384)                                                         1514   butyl 8α-methyl-                                                                        butyl 8α-methyl-9-oxo-                                  9-oxo-11α,5-di-                                                                         15-hydroxy-8-iso-10,13-                                       hydroxy-8-iso-13-                                                                             cis-prostadienoate                                            cis-prostenoate                                                               (Example 1384)                                                         1515   decyl 8β-methyl-                                                                         decyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-10,13-trans,-                                      hydroxy-13-trans-                                                                             17-cis-prostatrienoate                                        17-cis-prostadi-                                                              enoate (Example                                                               1385)                                                                  1516   decyl 8α-methyl-                                                                        decyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-8-iso-10,-                                         hydroxy-8-iso-  13-trans,17-cis-prosta-                                       13-trans,17-cis-                                                                              trienoate                                                     prostadienoate                                                                (Example 1385)                                                         1517   decyl 8β-methyl-                                                                         decyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-10,13-cis-                                         hydroxy-13-cis- 17-cis-prostatrienoate                                        17-cis-prostadi-                                                              enoate (Example                                                               1385)                                                                  1518   decyl 8α-methyl-                                                                        decyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-8-iso-10,13-                                       hydroxy-8-iso-13-                                                                             cis-17-cis-prostatrie-                                        cis-17-cis-pro- noate                                                         stadienoate                                                                   (Example 1385)                                                         1519   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α-ace-                                                                          15-hydroxy-10,13-trans-                                       toxy-15-hydroxy-                                                                              prostadienoate                                                13-trans-proste-                                                              noate (Example                                                                1386)                                                                  1520   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α-ace-                                                                          15-hydroxy-8-iso-10,13-                                       toxy-15-hydroxy-                                                                              trans-prostadienoate                                          8-oxo-13-trans-                                                               prostenoate                                                                   (Example 1386)                                                         1521   ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α-ace-                                                                          15-hydroxy-10,13-cis-                                         toxy-15-hydroxy-                                                                              prostadienoate                                                13-cis-proste-                                                                noate (Example                                                                1386)                                                                  1522   ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α-ace-                                                                          15-hydroxy-8-iso-10,13-                                       toxy-15-hydroxy-                                                                              cis-prostadienoate                                            8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1386)                                                         ______________________________________                                    

EXAMPLES 1523-1654

Treatment of the designated 9-oxo-prostenoic acid and ester derivativeslisted in Table 42 below with sodium borohydride in ethanol as describedin Example 257 gives the product 9α and 9β hydroxy derivatives of thetable, which are separable by standard chromatographic technique.

                  TABLE 42                                                        ______________________________________                                              Starting 8-       Product                                                     methyl-9-oxo      8-methyl-9α/β,-                                  11α,15-di-  11α,15-trihydroxy-                              Ex-   hydroxy-13-prosten-                                                                             13-prostenoic                                         ample oic acid or ester acid or ester                                         ______________________________________                                        1523  8β-methyl-prosta-                                                                          8β-methyl-prosta-                                      glandin E.sub.1   glandin F.sub.1 α/F.sub.1 β                      (Example 1353)                                                          1524  8α-methyl-8-iso-                                                                          8α-methyl-8-iso-pros-                                 prostaglandin E.sub.1                                                                           taglandin F.sub.1 α/F.sub.1 β                    (Example 1353)                                                          1525  8β-methyl-9-oxo-11α-                                                                 8β-methyl-9α/β,11α,-                  15-dihydroxy-13-cis-                                                                            15-trihydroxy-13-                                           prostenoic acid   cis-prostenoic acid                                         (Example 1353)                                                          1526  8α-methyl-9-oxo-                                                                          8α-methyl-9α/β,11α,                  11α,15-dihydroxy-                                                                         15-trihydroxy-8-iso-                                        8-iso-13-cis-pros-                                                                              13-cis-prostenoic                                           tenoic acid       acid                                                        (Example 1353)                                                          1527  8β-methyl-9-oxo-                                                                           8β-methyl-9α/β,11α,-                  11α,15-dihydroxy-                                                                         15-trihydroxy-16,16-                                        16,16-dimethyl-13-                                                                              dimethyl-13-trans-                                          trans-prostenoic  prostenoic acid                                             acid                                                                          (Example 1354)                                                          1528  8α-methyl-9-oxo-                                                                          8α-methyl-9α/β,11α,-                 11α,15-dihydroxy-                                                                         15-trihydroxy-16,16-                                        16,16-dimethyl-8- dimethyl-8-iso-13-                                          iso-13-trans-pros-                                                                              trans-prostenoic acid                                       tenoic acid                                                                   (Example 1354)                                                          1529  8β-methyl-9-oxo-                                                                           8β-methyl-9α/β,11α-                   11α,15-dihydroxy-                                                                         15-trihydroxy-16,16-                                        16,16-dimethyl-13-,                                                                             dimethyl-13-cis-                                            cis-prostenoic acid                                                                             prostenoic acid                                             (Example 1354)                                                          1530  8α-methyl-9-oxo-                                                                          8α-methyl-9α/β,11α,                  11α ,15-dihydroxy-                                                                        15-trihydroxy-16,16-                                        16,16-dimethyl-8- dimethyl-8-iso-13-                                          iso-13-cis-pros-  cis-prostenoic acid                                         tenoic acid                                                                   (Example 1354)                                                          1531  8β-methyl-9-oxo-11α-                                                                 8β-methyl-9α/β,11α,-                  15-dihydroxy-17,17-                                                                             15-trihydroxy-17,17-                                        dimethyl-13-trans-                                                                              dimethyl-13-trans-                                          prostenoic acid   prostenoic acid                                             (Example 1355)                                                          1532  8α-methyl-9-oxo-                                                                          8α-methyl-9α/β,11α,-                 11α,15-dihydroxy-8-                                                                       15-trihydroxy-17,17-                                        iso-17,17-di-     dimethyl-8-iso-13-                                          methyl-13-trans-  trans-prostenoic                                            prostenoic acid   acid                                                        (Example 1355)                                                          1533  8β-methyl-9-oxo-                                                                           8β-methyl-9α/β,11α-                   11α,15-dihydroxy-17,                                                                      15-trihydroxy-17,17-                                        17-dimethyl-13-cis-                                                                             dimethyl-13-cis-                                            prostenoic acid   prostenoic acid                                             (Example 1355)                                                          1534  8α-methyl-9-oxo-                                                                          8α-methyl-9α/β,11α,-                 11α,15-dihydroxy-                                                                         15-trihydroxy-8-iso-                                        17,17-dimethyl-8- 17,17,dimethyl-13-                                          iso-13-cis-pros-  cis-prostenoic                                              tenoic acid       acid                                                        Example1355)                                                            1535  8β-methyl-9-oxo-11α-                                                                 8β-methyl-9α/β,11α-                   15-dihydroxy-13-  15-trihydroxy-13-                                           trans-17-cis-pro- trans,17-cis-pros-                                          stadienoic acid   tadienoic acid                                              (Example 1356)                                                          1536  8α-methyl-9-oxo-11α-                                                                8α-methyl-9α/β,11α,-                 15-dihydroxy-8-iso-                                                                             15-trihydroxy-8-iso-                                        13-trans,17-cis-  13-trans-17-cis-                                            prostadienoic acid                                                                              prostadienoic acid                                          (Example 1356)                                                          1537  8β-methyl-9-oxo-11α-                                                                 8β-methyl-9α/β,11α,-                  15-dihydroxy-13-cis,                                                                            15-trihydroxy-13-cis,                                       17-cis-prostadienoic                                                                            17-cis-prostadienoic                                        acid              acid                                                        (Example 1356)                                                          1538  8α-methyl-9-oxo-11α-                                                                8α-methyl-9α/β,11α,-                 5-dihydroxy-8-iso-                                                                              15-trihydroxy-8-iso-                                        13-trans-17-cis-  13-cis,17-cis-pros-                                         prostadienoic acid                                                                              tadienoic acid                                              (Example 1356)                                                          1539  8β-methyl-9-oxo-11α -                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-20-  15-trihydroxy-20-                                           ethyl-13-trans-pros-                                                                            ethyl-13-trans-pros-                                        tenoic acid       tenoic acid                                                 (Example 1357)                                                          1540  8α-methyl-9-oxo-11α-                                                                8α-methyl-9α/β,11α,-                 15-dihydroxy-20-  15-trihydroxy-20-                                           ethyl-8-iso-13-trans-                                                                           ethyl-8-iso-13-                                             prostenoic acid   trans-prostenoic                                            (Example 1357)    acid                                                  1541  8β-methyl-9-oxo-11α-                                                                 8β-methyl-9α/β,11α,-                  15-dihydroxy-20-eth-                                                                            15-trihydroxy-20-                                           yl-13-cis-prostenoic                                                                            ethyl-13-cis-pro-                                           acid              stenoic acid                                                (Example 1357)                                                          1542  8α-methyl-9-oxo-11α-                                                                8α-methyl-9α/β,11α,-                 15-dihydroxy-20-  15-trihydroxy-20-                                           ethyl-8-iso-13-cis-                                                                             ethyl-8-iso-13-cis-                                         prostenoic acid   prostenoic acid                                             (Example 1357)                                                          1543  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-6,7- 15-trihydroxy-6,7-                                          dinor-13-trans-pros-                                                                            dinor-13-trans-pros-                                        tenoic acid       tenoic acid                                                 (Example 1358)                                                          1544  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-6,7- 15-trihydroxy-6,7-                                          dinor-8-iso-13-trans-                                                                           dinor-8-iso-13-                                             prostenoic acid   trans-prostenoic                                            (Example 1358)    acid                                                  1545  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-6,7- 15-trihydroxy-6,7-                                          dinor-13-cis-     dinor-13-cis-                                               prostenoic acid   prostenoic acid                                             (Example 1358)                                                          1546  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-6,7- 15-trihydroxy-6,7-                                          dinor-8-iso-13-cis-                                                                             dinor-8-iso-13-cis-                                         prostenoic acid   prostenoic acid                                             (Example 1358)                                                          1547  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-5,6,7-                                                                             15-trihydroxy-5,6,7-                                        trinor-20-methyl-13-                                                                            trinor-20-methyl-13-                                        trans-prostenoic acid                                                                           trans-prostenoic acid                                       (Example 1359)                                                          1548  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-5,6,7-                                                                             15-trihydroxy-5,6,7-                                        trinor-20-methyl-8-                                                                             trinor-20-methyl-8-                                         iso-13-trans-pros-                                                                              iso-13-trans-prosten-                                       tenoic acid       oic acid                                                    (Example 1359)                                                          1549  8β-methyl-9-oxo-11α-                                                                 8β-methyl-9α/β,11α,-                  15-dihydroxy-5,6,7,-                                                                            15-trihydroxy-5,6,7-                                        trinor-20-methyl- trinor-20-methyl-13-                                        13-cis-prostenoic cis-prostenoic acid                                         acid                                                                          (Example 1359)                                                          1550  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-5,6,7-                                                                             15-trihydroxy-5,6,7-                                        trinor-20-methyl-8-                                                                             trinor-20-methyl-8-                                         iso-13-cis-prosten-                                                                             iso-13-cis-prosten-                                         oic acid          oic acid                                                                      (Example 1359)                                        1551  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-7a,7b-                                                                             15-trihydroxy-7a,7b-                                        bishomo-13-trans- bishomo-13-trans-                                           prostenoic acid   prostenoic acid                                             (Example 1360)                                                          1552  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-7a,7b-                                                                             15-trihydroxy-7a,7b-                                        bishomo-8-iso-13- bishomo-8-iso-13-                                           trans-prostenoic  trans prostenoic                                            acid              acid                                                        (Example 1360)                                                          1553  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-7a,7b-                                                                             15-trihydroxy-7a,7b-                                        bishomo-13-cis-   bishomo-13-cis-pro-                                         prostenoic acid   stenoic acid                                                (Example 1360)                                                          1554  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-7a,7b-                                                                             15-trihydroxy-7a,7b-                                        bishomo-8-iso-13- bishomo-8-iso-13-cis-                                       cis-prostenoic acid                                                                             prostenoic acid                                             (Example 1360)                                                          1555  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α-                   15-dihydroxy-2-eth-                                                                             15-trihydroxy-2-                                            yl-13-tfrans-prosten-                                                                           ethyl-13-trans-                                             oic acid          prostenoic acid                                             (Example 1360)                                                          1556  8α-methyl-9-oxo-11α,-                                                               8α- methyl-9α/β,11α,-                yl-8-iso-13-trans-                                                                              ethyl-8-iso-13-trans-                                       prostenoic acid   prostenoic acid                                             (Example 1361)                                                          1557  8β-methyl-9-oxo-11α  ,-                                                              8β-methyl-9α/β,11α,-                  15-dihydroxy-2-ethyl-                                                                           15-trihydroxy-2-                                            13-cis-prostenoic ethyl-13-cis-pro-                                           acid              stenoic acid                                                (Example 1361)                                                          1558  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α-                  15-dihydroxy-2-   15,trihydroxy-2-                                            ethyl-8-iso-13-cis-                                                                             ethyl-8-iso-13-cis-                                         prostenoic acid   prostenoic acid                                             (Example 1361)                                                          1559  8β-metjyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3,3,20-                                                                            15-trihydroxy-3,3,20-                                       trimethyl-8-iso-13-                                                                             trimethyl-13-trans-                                         trans-prostenoic  prostenoic acid                                             acid (Example 1362)                                                     1560  8α-methyl-9-oxo-11α-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3,3,20-                                                                            15-trihydroxy-3,3                                           trimethyl-8-iso-13-                                                                             20-trimethyl-8-iso-                                         trans-prostenoic ac                                                                             13-trans-prostenoic                                         acid (Example 1362)                                                                             acid                                                  1561  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3,3,20-                                                                            15-trihydroxy-3,3                                           (Example 20-trimethyl-13-cis-                                                 prostenoic acid   prostenoic acid                                             (Example 1362)                                                          1562  (α-methyl-9-oxo-11α,-                                                               8α-methyl-9α1β,11α,-                 15-dihydroxy-3,3,20-                                                                            15-trihydroxy-3,3,20-                                       trimethyl-8-iso-13-                                                                             trimethyl-8-iso-13-                                         cis-prostenoic acid                                                                             cis-prostenoic acid                                         (Example 1362)                                                          1563  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        (Example 13-trans-prostenoic                                                  acid              acid                                                        (Example 1363)                                                          1564  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        8-iso-13-trans-   8-iso-13-trans-                                             prostenoic acid   prostenoic acid                                             (Example 1363)                                                          1565  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-(                                                                            15-trihydroxy-3-oxa-                                        8-iso-13-cis-pro- 8-iso-13-cis-pro-                                           stenoic acid                                                            1575                                                                                (Example 1363)                                                          1566  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        8-iso-13-cis-pro- 8-iso-13-cis-pro-                                           stenoic acid      stenoic acid                                                (Example 1363)                                                          1567  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        16,16-dimethyl-13-                                                                              16,16-dimethyl-13-                                          trans-prostenoic  trans-prostenoic                                            acid              acid                                                        (Example 1364)                                                          1568  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-3-oxa-                                                                             5-trihydroxy-3-oxa-                                         16,16-dimethyl-8- 16,16-dimethyl-8-                                           iso-13-trans-pro- iso-13-trans-pro-                                           stenoic acid      stenoic acid                                                (Example 1364)                                                          1569  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α,β-11α,-                  15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        16,16-dimethyl-13-                                                                              16,16-dimethyl-13-                                          cis-prostenoic acid                                                                             cis-prostenoic acid                                         (Example 1364)                                                          1570  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β-11α,-                 15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        16,16-dimethyl-8- 16,16-dimethyl-8-                                           iso-13-cis-pro-   iso-13-cis-pro-                                             stenoic acid      stenoic acid                                                (Example 1364)                                                          1571  8α-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        13-trans,17-cis-  13-trans,17-cis-                                            prostadienoic acid                                                                              prostadienoic acid                                          (Example 1365)                                                          1572  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        8-iso-13-trans,17-                                                                              8-iso-13-trans,17-                                          cis-prostadienoic cis-prostadienoic                                           acid              acid                                                        (Example) 1365)                                                         1573  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        13-cis,17-cis-pros-                                                                             13-cis,17-cis-                                              stadienoic acid   prostadienoic acid                                          (Example 1365)                                                          1574  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        8-iso-13-cis,17-cis-                                                                            8-iso-13-cis,17-cis-                                        prostadienoic acid                                                                              prostadienoic acid                                          (Example 1365)                                                          1575  8β-methyl-9-oxo-11α,-                                                                8β-methnyl-9c-60 /β.11α,-                   15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        20-ethyl-13-trans-                                                                              20-ethyl-13-trans-                                          prostenoic acid   prostenoic acid                                             (Example 1366)                                                          1576  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        20-ethyl-8-iso-13-                                                                              20-ethyl-8-iso-13-                                          trans-prostenoic  trans-prostenoic                                            acid              acid                                                        (Example 1366)                                                          1577  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        20-ethyl-13-cis-  20-ethyl-13-cis-                                            prostenoic acid   prostenoic acid                                       (Example 1366)                                                                1578  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9-60 /β,11α,-                    15-dihydroxy-3-oxa-                                                                             15-trihydroxy-3-oxa-                                        20-ethyl-8-iso-13-                                                                              20-ethyl-8-iso-13-                                          cis-prostenoic acid                                                                             cis-prostenoic acid                                         (Example 1366)                                                          1579  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-2-flu-                                                                             15-trihydroxy-2-                                            oro-17,17-dimethyl-                                                                             fluoro-17,17-dimeth-                                        13-trans-prostenoic                                                                             yl-13-trans-prosten-                                        acid              oic acid                                                    (Example 1367)                                                          1580  8α-methyl-9-oxo,11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-2-flu-                                                                             15-trihydroxy-2-                                            oro-17,17-dimethyl-                                                                             fluoro-17,17-dimeth-                                        8-iso-13-trans-   yl-8-iso-13-trans-                                          prostenoic acid   prostenoic acid                                             (Example 1367)                                                          1581  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-2-   15-trihydroxy-2-                                            fluoro-17,17-di-  fluoro-17,17-dimeth-                                        methyl-13-cis-pros-                                                                             yl-13-cis-prostenoic                                        tenoic acid       acid                                                        (Example 1367)                                                          1582  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-2-flu-                                                                             15-trihydroxy-2-                                            oro-17,17-dimethyl-                                                                             fluoro-17,17-dimeth-                                        8-iso-13-cis-pros-                                                                              yl-8-iso-13-cis-                                            tenoic acid       prostenoic acid                                             (Example 1367)                                                          1583  8β-methyl-9-oso-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-7-nor-                                                                             15-trihydroxy-7-nor-                                        13-trans-prostenoic                                                                             13-trans-prostenoic                                         acid              acid                                                        (Example 1368)                                                          1584  8α-metnhyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                 15-dihydroxy-7-nor-                                                                             15-trihydroxy-7-nor-                                        8-iso-13-trans-pros-                                                                            8-iso-13-trans-pros-                                        tenoic acid       tenoic acid                                                 (Example 1368)                                                          1585  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-7-nor-                                                                             15-trihydroxy-7-nor-                                        13-cis-prostenoic 13-cis-prostenoic - acid acid                               (Example 1368)                                                          1586  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-7-nor-                                                                             15-trihydroxy-7-nor-                                        8-iso-13-cis-prosten-                                                                           8-iso-13-cis-pro-                                           oic acid          stenoic acid                                                (Example 1368)                                                          1587  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-7a-homo-                                                                           15-trihydroxy-7a-                                           16,16-dimethyl-13-                                                                              homo-16,16-di8methyl-                                       trans-prostenoic  13-trans-prostenoic                                         acid              acidf                                                       (Example 1369)                                                          1588  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-7a-  15-trihydroxy-7a-                                           homo-16,16-dimethyl-                                                                            homo-16,16-dimethyl-                                        8-iso-13-trans-pros-                                                                            8-iso-13-trans-pro-                                         tenoic acid       stenoic acid                                                (Example 1369)                                                          1589  8β-methyl-9-oxo-11α,-                                                                8β-methyl-98α/β,11α,-                 15-dihydroxy-7a-  15-drihydroxy-7a-                                           homo-16,16-dimethyl-                                                                            homo-16,16-dimethyl-                                        13-cis-prostenoic 13-cis-prostenic                                            acid acid                                                                     (Example 1369)                                                          1590  8α-methyl-9-oso-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-7a-  15-trihydroxy-7a-                                           homo-16,16-dimethyl-                                                                            homo-16,16-dimethyl-                                        8-iso-13-cis-prosten-                                                                           8-iso-13-cis-pros-                                          oic acid          tenoic acid                                                 (Example 1369)                                                          1591  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-2-phen-                                                                            15-trihydroxy-2-                                            yl-13-trans-prosten-                                                                            phenyl-13-trans-pros-                                       oic acid          tenoic acid                                                 (Example 1370)                                                          1592  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-2-phen-                                                                            15-trihydroxy-2-phen-                                       yl-8-iso-13-trans-                                                                              yl-8-iso-13-trans-                                          prostenoic acid   prostenoic acid                                             (Example 1370)                                                          1593  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-2-phen-                                                                            15-trihydroxy-2-phen-                                       yl-13-cis-prostenoic                                                                            yl-13-cis-prostenoic                                        acid              acid                                                        (Example 1370)                                                          1594  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-2-phen-                                                                            15-trihydroxy-2-                                            yl-8-iso-13-cis-  phenyl-8-iso-13-cis-                                        prostenoic acid   prostenoic acid                                             (Example 1370)                                                          1595  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-2-meth-                                                                            15-trihydroxy-2-meth-                                       yl-13-trans-17-cis-                                                                             yl-13-trans,17-cis-                                         prostadienoic acid                                                                              . prostadienoic acid                                        (Example 1371)                                                          1596  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-2-   15-trihydroxy-2-meth-                                       methyl-8-iso-13-  yl-8-iso-13-                                                trans,17-cis-prosta-                                                                            cis-                                                        dienoic acid      acid                                                        (Example 1371)                                                          1597  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-2-meth-                                                                            15-trihydroxy-2-                                            yl-13-cis,17-cis- methyl-13-cis,17-cis-                                       prostadienoic acid. prostadienoic acid                                        (Example 1371)                                                          1598  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-2-   15-trihydroxy-2-meth-                                       methyl-8-iso-13-cis,                                                                            yl-8-iso-13-cis,17-                                         17-cis-prostadienoic                                                                            cis-prostadienoic                                           acid (Example 1371)                                                                             acid                                                  1599  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-5,cis-                                                                             15-trihydroxy-5 cis-                                        13-trans-prosta-  13-trans-prostadien-                                        dienoic acid      oic acid                                                    (Example 1372)                                                          1600  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-8-iso-                                                                             15-trihydroxy-8-iso-                                        5-cis-13-trans-pros-                                                                            5 cis,13-trans-pros-                                        tadienoic acid    tadienoic acid                                              (Example 1372)                                                          1601  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-5-cis,                                                                             15-trihydroxy-5 cis-                                        13-cis-prostadien-                                                                              13-cis-prostadienoic                                        oic acid          acid                                                        (Example 1372)                                                          1602  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-8-iso-                                                                             15-trihydroxy-8-iso-                                        5-cis-13-cis-prosta-                                                                            5 cis 13-cis-prosta-                                        dienoic acid      dienoic acid                                                (Example 1372)                                                          1603  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-5-cis,-                                                                            15-trihydroxy-5-cis,-                                       13-trans,17-cis-  13-trans,17-cis-                                            prostatrienoic acid                                                           (Example 1373)                                                          1604  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-8-iso-                                                                             15-dihydroxy-8-iso-                                         5-cis,13-trans,17-                                                                              5-cis,13-trans,17-                                          cis-prostatienoic cis-prostatrienoic                                          acid              acid                                                        (Example 1373)                                                          1605  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-5-cis,-                                                                            15-trihydroxy-5-cis,-                                       13-cis,17-cis-prosta-                                                                           13-cis,17-cis-                                              trienoic acid. prostatrienoic acid                                            (Example 1373)                                                          1606  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-8-iso-                                                                             15-trihydroxy-8-iso-                                        5-cis,13-cis,17-  5-cis,13-cis,17-cis-                                        cis-prostatrienoic                                                                              prostatrienoic acid                                         acid                                                                          (Example 1373)                                                          1607  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-16,16-                                                                             15-trihydroxy-16,16-                                        dimethyl-5-cis,13-                                                                              dimethyl-5-cis,13-                                          trans-prostadienoic                                                                             trans-prostadienoic                                         (Example 1374)    acid                                                  1608  8α-methyl-9-oxo-11α,-                                                               8α-methyl-09α/β,11α,-                15-dihydroxy-16,16-                                                                             15-trihydroxy-16,16-                                        dimethyl-8-iso-5- dimethyl-8-iso-5-cis-                                       cis,13-trans-prosta-                                                                            13-trans-prostadien-                                        dienoic acid      oic acid                                                    (Example 1374)                                                          1609  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-16,16-                                                                             15-trihydroxy-16,16-                                        dimethyl-5-cis-   dimethyl-5-cis,13-                                          13-cis-prostadienoic                                                                            cis-prostadienoic                                           acid              acid                                                        (Example 1374)                                                          1610  8α-methyl-9-oxo-11α,-                                                               8α-methylk-9α/β,11α,-                15-dihydroxy-16,16-                                                                             15-trihydroxy-16,16-                                        dimethyl-8-iso-5-cis-                                                                           dimethyl-8-iso-5-cis-                                       13-cis-prostadienoic                                                                            13-cis-prostadienoic                                        acid (Example 1374)                                                                             acid                                                  1611  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4-nor-                                                                             15-trihydroxy-4-nor-                                        20-methyl-5-cis,13-                                                                             20-methyl-5-cis,13-                                         trans-prostadienoic                                                                             trans-prostadienoic                                         acid              acid                                                        (Example 1375)                                                          1612  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α  /β,11α,-               15-dihydroxy-4-nor-                                                                             15-trihydroxy-4-nor-                                        20-methyl-8-iso-5-                                                                              20-methyl-8-iso-                                            cis,13-trans-pros-                                                                              5-cis,13-trans-                                             tadienoic acid    prostadienoic acid                                          (Example 1375)                                                          1613  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4-nor-                                                                             15-trihydroxy-4-nor-                                        20-methyl-5-cis,13-                                                                             20-methyl-5-cis,13-                                         cis-prostadienoic cis-prostadienoic                                           acid              acid                                                        (Example 1375)                                                          1614  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-4-nor-                                                                             15-trihydroxy-4-nor-                                        20-methyl-8-iso-5-                                                                              20-methyl-8-iso-5-                                          cis,13-cis-prosta-                                                                              cis,13-cis-prosta-                                          dienoic acid      dienoic acid                                                (Example 1375)                                                          1615  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4a-homo-                                                                           15-trihydroxy-4a-                                           17,17-dimethyl-5-cis-                                                                           homo-17,17-dimethyl-                                        13-trans-prostadien-                                                                            5-cis,13-trans-pros-                                        oic acid          tadienoic aCID                                              (Example 1376)                                                          1616  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-4a-homo-                                                                           15-trihydroxy-4a-                                           17,17-dimethyl-8- homo-17,17-dimethyl-                                        iso-5-cis,13-trans-                                                                             8-iso-5-cis,13-cis-                                         prostadienoic acid                                                                              prostadienoic acid                                          (Example 1376)                                                          1617  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4a-homo-                                                                           15-trihydroxy-4a-                                           17,17-dimethyl-5-cis-                                                                           homo-17,17-dimethyl-                                        13-cis-prostadienoic                                                                            5-cis,13-cis-prosta-                                        acid              dienoic acid                                                (Example 1376)                                                          1618  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-4a-homo-                                                                           15-trihydroxy-4a-                                           17,17-dimethyl-8-iso-                                                                           homo-17,17-dimethyl-                                        5-cis,13-cis-prosta-                                                                            8-iso-5-cis,13-cis-                                         dienoic acid      prostadienoic acid                                          (Example 1376)                                                          1619  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4a,4b-                                        bishomo-20-ethyl-5-                                                                             bishomo-20-ethyl-                                           cis,13-trans-prosta-                                                                            5-cis,13-trans-pros-                                        dienoic acid. tadienoic acid                                                  (Example 1377)                                                          1620  8 60 -methyl-9-oxo-11α,-                                                                  8α-methyl-9α  1β,11α,-               15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4a,4b-                                        bishomo-20-ethyl-8-                                                                             bishomo-20-ethyl-8-                                         iso-54-cis,13-trans-                                                                            iso-5-cis,13-trans-                                         prostadienoic acid                                                                              prostadienoic acid                                          (Example 1377)                                                          1621  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4a,4b-                                        bishomo-230-ethyl-5-                                                                            bishomo-20-ethyl-5-                                         cis,13-cis-prosta-                                                                              cis,13-cis-prosta-                                          dienoic acid      dienoic aci                                                 (Example 1377)                                                          1622  8α-methyl-9-oxo-11α,- 8α-methyl-9α/β,11          α,-                                                                     15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4z,4b-                                        bishomo-20-ethyl-8-                                                                             bishomo-20-ethyl-8-                                         iso-5-cis,13-cis- iso-5-cis,13-cis-                                           prostadienoic acid                                                                              prostadienoic                                               (Example 1377)                                                          1623  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4a,4b-                                        bis-homo-5-cis,13-                                                                              bishomo-5-cis,13-                                           trans,17-cis-prosta-                                                                            trans,17-cis-prosta-                                        trienoic acid     trienoic acid                                               (Example 1378)                                                          1624  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4a,4b-                                        bis-homo-8-iso-5-cis-                                                                           bis-homo-8-iso-5-cis,-                                      13-trans,17-cis-pros-                                                                           13-trans,17-cis-                                            tatrienoic acid   prostatrienoic aCID                                         (Example 1378)                                                          1625  8β-methyl-9-oxo-11α,-                                                                8β-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4a,4b-                                        bis-homo-5-cis,13-                                                                              bis-homo-5-cis,13-                                          cis,17-cis-pros-  cis-17-cis-prosta-                                          tatrienoic acid   trienoic acid                                               (Example 1378)                                                          1626  8α-methyl-9-oxo-11α,-                                                               8α-methyl-9α/β,11α,-                 15-dihydroxy-4a,4b-                                                                             15-trihydroxy-4a,4b-                                        bis-homo-8-iso-5-cis,                                                                           bis-homo-8-iso-5-                                           13-cis,17-cis-pros-                                                                             cis,13-cis,17-cis-                                          tatrienoic acid   prostatrienoic acid                                         (Example 1378)                                                          1627  8β-methyl-9- methyl 8β-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           20-methyl-13-trans-                                                                             hydroxy-20-methyl-                                          prostenoate       13-trans-prostenoate                                        (Example 1379(                                                          1628  methyl 8α-methyl-9-                                                                       methyl 8α-methyl-                                     oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           20-methyl-8-iso-13-                                                                             hydroxy-20-methyl-                                          trans-prostenoate 8-iso-13-trans-pros-                                        (Example 1379)    tenoate                                               1629  methyl 8β-methyl-9-                                                                        methyl 8β-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           20-methyl-13-cis- hydroxy-20-methyl-                                          prostenoate       13-cis-prostenoate                                          (Example 1379)                                                          1630  methyl 8α-methyl-9-                                                                       methyl 8α                                             oxo-11α,15-dihydroxy-                                                                     9α/β,15-tri-                                     20-methyl-8-iso-13-                                                                             hydroxy-20-methyl-                                          cis-prostenoate   8-iso-13-cis-pros-                                          (Example 1379)    tenoate                                               1631  ethyl 8β-methyl-9-                                                                         ethyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,15-tri-                                     7a,7b-bis-homo-13-                                                                              hydroxy-7a,7b-bis-                                          trans,17-cis-prosta-                                                                            homo-13-trans,17-                                           dienoate          cis-prostadienoate                                          (Example 1380)                                                          1632  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-9α/                             oxo-11-60 ,15-dihydroxy-                                                                        β,11α,15-trihydroxy                              7a,7b-bis-homo-8-iso-                                                                           7a,7b-bis-homo-8-                                           13-trans-17-cis-  iso-13-trans,17-cis-                                        prostadienoate    prostadienoate                                              (Examplew 1380)                                                         1633  ethyl 8β-methyl-9-                                                                         ethyl 8β-methyl-                                       7a,7b-bis-homo-13-                                                                              hydroxy-7a,7b-bis-                                          cis,17-cis-prosta-                                                                              homo-13-cis,17-cis-                                         dienoate          prostadienoate                                              (Example 1380)                                                          1634  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9αβ,11α,15-tri-                            7a,7b-bis-homo-8- hydroxy-7a,7b-bis-                                          iso-13-cis,17-cis-                                                                              homo-8-iso-13-cis-                                          prostadienoate    17-cis-prosta-                                              (Example 1380)    dienoate                                              1635  ethyl 8β-methyl-9-                                                                         ethyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           2-ethyl-16,16-dimeth-                                                                           hydroxy-2-ethyl-16,                                         yl-13-tfrans-prosten-                                                                           16-methyl-13-                                               oate              trans-prostenoate                                           (Example 1381)                                                          1636  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           2-ethyl-16,16-di- hydroxy-2-ethyl-                                            methyl-8-iso-13-  16,16-dimethyl-8-                                           trans-prostenoate. iso-13-trans-pros-                                         (Example 1381)    tenoate                                               1637  ethyl 8β -methyl-9-                                                                        ethyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           2-ethyl-16,16-di- hydroxy-2-ethyl-                                            methyl-13-cis-pros-                                                                             16,16-dimethyl-13-                                          tenoate           cis-prostenoate                                             (Example 1381)                                                          1638  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-trti-                          2-ethyl-16,16-di- hydroxy-2-ethyl-16,                                         methyl-8-iso-13-cis-                                                                            16-dimethyl-8-iso-                                          prostenaote       13-cis-prostenoate                                          (Example 1381)                                                          1639  ethyl 8β-methyl-9-                                                                         ethyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3,3,17,17-tetra-  hydroxy-3,3,17,17-                                          methyl-13-trans-  tetramethyl-13-                                             prostenoate       trans-prostenoate                                           (Example 1382)                                                          1640  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3,3,17,17-tetra-  hydroxy-3,3,17,17-                                          methyl-8-iso-13-  tetramethyl-8-iso-                                          trans-prostenoate 13-trans-prosten-                                           (Example 1382)    oate                                                  1641  ethyl 8β-methyl-9-                                                                         ethyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3,3,17,17-tetramethyl-                                                                          hydroxy-3,3,17,17-                                          13-cis-prostenoate                                                                              tetramethyl-13-cis-                                         (Example 1382)    prostenoate                                           1642  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3,3,17,17-tetramethy;-                                                                          hydroxy-3,3,17,17-                                          8-iso-13-cis-prosten-                                                                           tetramethyl-8-iso-                                          oate              13-cis-prostenoate                                          (Example 1382)                                                          1643  ethyl 8β-methyl-9-                                                                         ethyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3-osa-17,17-dimethyl-                                                                           hydroxy-3-oxa-17,17-                                        13-trans-prostenoate                                                                            dimethyl-13-trans-                                          (Example 1383)    prostenoate                                           1644  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3-oxa-17,17-dimethyl-                                                                           hydroxy-3-oxa-17,17-                                        8-iso-13-trans-pros-                                                                            dimethyl-8-iso-13-                                          tenoate           trans-prostenoate                                           (Example 1383)                                                          1645  ethyl 8β-methyl-9-                                                                         ethyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3-oxa-17,17-dimethyl-                                                                           hydroxy-3-oxa-17,17-                                        13-cis-prostenoate                                                                              dimethyl-13-cis-                                            (Example 1383)    prostenoate                                           1646  ethyl 8α-methyl-9-                                                                        ethyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           3-oxa-17,17-dimethyl-                                                                           hydroxy-3-oxa-17,17-                                        8-iso-13-cis-pros-                                                                              dimethyl-8-iso-13-                                          tenoate           cis-prostenoate                                             (Example 1383)                                                          1647  butyl 8β-methyl-9-                                                                         butyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           13-trans-prostenoate                                                                            hydroxy-13-trans-                                           (Example 1384)    prostenoate                                           1648  butyl 8α-methyl-9-                                                                        butyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           8-iso-13-trans-   hydroxy-8-iso-13-                                           prostenoate       trans-prostenoate                                           (Example 1384)                                                          1649  butyl 8β-methyl-9-                                                                         butyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           13-cis-prostenoate                                                                              hydroxy-13-cis-                                             (Example 1384)    prostenoate                                           1650  butyl 8α-methyl-9-                                                                        butyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           8-iso-13-cic-pros-                                                                              hydroxy-8-iso-13-                                           tenoate           cis-prostenoate                                             (Example 1384)                                                          1651  decyl 8β-methyl-9-                                                                         decyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-trti-                          13-trans,17-cis-  hydroxy-13-trans,-                                          prostadienoate    17-cis-prosta-                                              (Example 1385)    dienoate                                              1652  decyl 8α-methyl-9-                                                                        decyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           8-iso-13-trans,17-                                                                              hydroxy-8-iso-13-                                           cis-prostadienoate                                                                              trans,17-cis-pro-                                           (Example 1385)    stadienoate                                           1653  decyl 8β-methyl-9-                                                                         decyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                     9α/β,11α,15-tri-                           13-cis,17-cis-pros-                                                                             hydroxy-13-cis,17-                                          tadienoate        cis-prostadienoate                                          (Example 1385)                                                          1654  decyl 8α-methyl-9-                                                                        decyl 8α-methyl-                                      oxo-11α,15-dihydroxy                                                                      9α/β,11α,15-tri-                           8-iso-13-cis,17-cis-                                                                            hydroxy-8-iso-13-                                           prostadienoate    cis,17-cis-prosta-                                          (Example 1385)    dienoate                                              ______________________________________                                    

EXAMPLES 1655-1781

Saponification of the alkyl esters designated in Table 43 below by theprocedure described in Example 495 is productive of the carboxylic acidsof the table. The epimeric 9α and 9β hydroxy products are separable bythe usual chromatographic procedures.

                  TABLE 43                                                        ______________________________________                                        Ex-    Starting alkyl                                                         ample  prostenoate     Product prostenoic acid                                ______________________________________                                        1655   11-deoxy-8β-meth-                                                                        11-deoxy-8β-methyl-pros-                                 yl-prostaglandin                                                                              taglandin E.sub.1                                             E.sub.1 methyl ester -                                                                        (Example 1188)                                         1656   11-deoxy-8α-meth-                                                                       11-deoxy-8α-methyl-8-                                   yl-8-iso-prosta-                                                                              iso-prostaglandin E.sub.1                                     glandin E.sub.1 meth-                                                         yl ester (Exam-                                                               ple 1188)                                                              1657   methyl 15-hy-   15-hydroxy-8β-methyl-9-                                  droxy-8β-methyl                                                                          oxo-13-cis-prostenoic                                         9-oxo-13-cis-   acid                                                          prostenoate                                                                   (Example 1188)                                                         1658   methyl-15-hy-   15-hydroxy-8α-methyl-8-                                 droxy-8α-methyl-                                                                        iso-9-oxo-13-cis-                                             8-iso-9-oxo-13- prostenoic acid                                               cis-prostenoate                                                               (Example 1188)                                                         1659   11-deoxy-8β-meth-                                                                        11-deoxy-8β-methyl-                                      yl-prostaglandin                                                                              prostaglandin F.sub.1 α/β                          F.sub.1 α/β methyl                                                 esters (Ex. 1206)                                                      1660   11-deoxy-8α-meth-                                                                       11-deoxy-8α-methyl-8-                                   yl-8-iso-prosta-                                                                              iso-prostaglandin                                             glandin F.sub.1 α/β                                                                F.sub.1 α/β                                        methyl esters                                                                 (Example 1207)                                                         1661   methyl 9α,15-di-                                                                        9α,15-dihydroxy-8β-meth-                           hydroxy-8β-meth-                                                                         yl-13-cis-prostenoic                                          yl-13-cis-pros- acid                                                          tenoate (Example                                                              1208)                                                                  1662   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-16,16-dimethyl-13-                                      droxy-16,16-di  trans-prostenoic acid                                         methyl-13-trans-                                                              prostenoate                                                                   (Example 1190)                                                         1663   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-16,16-dimethyl-8-                                       droxy-16,16-di- iso-13-trans-prosten-                                         methyl-8-iso-13-                                                                              oic acid                                                      trans-prosteno-                                                               ate (Example                                                                  1190)                                                                  1664   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-16,16-dimethyl-                                         droxy-16,16-di- 13-cis-prostenoic acid                                        methyl-13-cis-                                                                prostenoate                                                                   (Example 1190)                                                         1665   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-16,16-dimethyl-                                         droxy-16,16-di- 8-iso-13-cis-prosten-                                         methyl-8-iso-13-                                                                              oic acid                                                      cis-prostenoate                                                               (Example 1190)                                                         1666   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-17,17-dimethyl-                                         droxy-17,17-di- 13-trans-prostenoic                                           methyl-13-trans-                                                                              acid                                                          prostenoate                                                                   (Example 1191)                                                         1667   ethyl 8α-methyl-                                                                        8αmethyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-17,17-dimethyl-                                         droxy-17,17-di- 8-iso-13-trans-pros-                                          methyl-8-iso-13-                                                                              tenoic acid                                                   trans-prosteno-                                                               ate (Example                                                                  1191)                                                                  1668   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-17,17-dimethyl-                                         droxy-17,17-di- 13-cis-prostenoic acid                                        methyl-13-cis-                                                                prostenoate                                                                   (Example 1191)                                                         1669   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-17,17-dimethyl-8-                                       droxy-17,17-di- iso-13-cis-prostenoic                                         methyl-8-iso-13-                                                                              acid                                                          cis-prostenoate                                                               (Example 1191)                                                         1670   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-13-trans,17-cis-                                        droxy-13-trans,-                                                                              prostadienoic acid                                            17-cis-prostadi-                                                              enoate (Example                                                               1192)                                                                  1671   ethyl 8αmethyl-                                                                         8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-13-trans,17-                                      droxy-8-iso-13- cis-prostadienoic acid                                        trans,17-cis-                                                                 prostadienoate                                                                (Example 1192)                                                         1672   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-13-cis,17-cis-                                          droxy-13-cis,17-                                                                              prostadienoic acid                                            cis-prostadien-                                                               oate (Example                                                                 1192)                                                                  1673   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-13-cis,17-                                        droxy-8-iso-13- cis-prostadienoic acid                                        cis,17-cis-pros-                                                              tadienoate (Ex-                                                               ample 1192)                                                            1674   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-13-trans-                                      droxy-20-ethyl-                                                               prostenoic acid                                                               13-trans-pros-                                                                tenoate (Example                                                              1193)                                                                  1675   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-13-                                      droxy-20-ethyl- trans-prostenoic acid                                         8-iso-13-trans-                                                               prostenoate                                                                   (Example 1193)                                                         1676   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-13-cis-                                        droxy-20-ethyl- prostenoic acid                                               13-cis-prosten-                                                               oate (Example                                                                 1193)                                                                  1677   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-13-                                      droxy-20-ethyl- cis-prostenoic acid                                           8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1193)                                                         1678   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7a,7b-bishomo-13-                                       droxy-7a,7b-bis-                                                                              trans-prostenoic acid                                         homo-13-trans-                                                                prostenoate                                                                   (Example 1195)                                                         1679   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7a,7b-bishomo-8-                                        droxy-7a,7b-bis-                                                                              iso-13-trans-prostenoic                                       homo-8-iso-13-  acid                                                          trans-prosteno-                                                               ate (Example                                                                  1195)                                                                  1680   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7a,7b-bishomo-13-                                       droxy-7a,7b-bis-                                                                              cis-prostenoic acid                                           homo-13-cis-                                                                  prostenoate                                                                   (Example 1195)                                                         1681   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7a,7b-bishomo-8-                                        droxy-7a,7b-bis-                                                                              iso-13-cis-prostenoic                                         homo-8-iso-13-  acid                                                          cis-prostenoate                                                               (Example 1195)                                                         1682   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2,20-bisethyl-13-                                       droxy-2,20-bis- trans-prostenoic acid                                         ethyl-13-trans-                                                               prostenoate                                                                   (Example 1196)                                                         1683   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2,20-bisethyl-8-                                        droxy-2,20-bis- iso-13-trans-prostenoic                                       ethyl-8-iso-13-                                                               trans-prosten-                                                                oate (Example                                                                 1196)                                                                  1684   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2,20-bisethyl-13-                                       droxy-2,20-bis- cis-prostenoic acid                                           ethyl-13-cis-                                                                 prostenoate                                                                   (Example 1196)                                                         1685   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2,20-bisethyl-8-                                        droxy-2,20-bis- iso-13-cis-prostenoic                                         ethyl-8-iso-13- acid                                                          cis-prostenoate                                                               (Example 1196)                                                         1686   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-13-trans-pros-                                         16-dimethyl-13- tenoic acid                                                   trans-prosteno-                                                               ate (Example                                                                  1197)                                                                  1687   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-8-iso-13-trans-                                        16-dimethyl-8-  prostenoic acid                                               iso-13-trans-                                                                 prostenoate                                                                   (Example 1197)                                                         1688   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-13-cis-prostenoic                                      16-mimethyl-13- acid                                                          cis-prostenoate                                                               (Example 1197)                                                         1689   ethyl 8α-methyl-                                                                        8αmethyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-8-iso-13-cis-                                          16-dimethyl-8-iso-                                                                            prostenoic acid                                               13-cis-prosteno-                                                              ate (Example 1197)                                                     1690   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-13-trans,-                                        droxy-3-oxa-13- 17-cis-prostadienoic                                          trans,17-cis-   acid                                                          prostadienoate                                                                (Example 1198)                                                         1691   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-3-oxa-8-iso-13-                                         droxy-3-oxa-8-  trans,17-cis-prostadi-                                        iso-13-trans,17-                                                                              enoic acid                                                    cis-prostadieno-                                                              ate (Example                                                                  1198)                                                                  1692   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-13-cis,17-                                        droxy-3-oxa-13- cis-prostadienoic acid                                        cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1198)                                                              1693   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-3-oxa-8-iso-13-                                         droxy-3-oxa-8-  cis,17-cis-prostadi-                                          iso-13-cis,17-  enoic acid                                                    cis-prostadieno-                                                              ate (Example                                                                  1198)                                                                  1694   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 13-trans-prostenoic                                           methyl-13-trans-                                                                              acid                                                          prostenoate                                                                   (Example 1199)                                                         1695   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 8-iso-13-trans-pros-                                          methyl-8-iso-   tenoic acid                                                   13-trans-pros-                                                                tenoate (Example                                                              1199)                                                                  1696   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 13-cis-prostenoic acid                                        methyl-13-cis-                                                                prostenoate                                                                   (Example 1199)                                                         1697   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 8-iso-13-cis-prosteno-                                        methyl-8-iso-   ic acid                                                       13-cis-prosten-                                                               oate (Example                                                                 1199)                                                                  1698   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-fluoro-17,17-di-                                      droxy-2-fluoro- methyl-13-trans-pros-                                         17,17-dimethyl- tenoic acid                                                   13-trans-pros-                                                                tenoate (Example                                                              1200)                                                                  1699   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2-fluoro-17,17-                                         droxy-2-fluoro- dimethyl-8-iso-13-                                            17,17-dimethyl- trans-prostenoic acid                                         8-iso-13-trans-                                                               prostenoate                                                                   (Example 1200)                                                         1700   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-fluoro-17,17-                                         droxy-2-fluoro- dimethyl-13-cis-                                              17,17-dimethyl- prostenoic acid                                               13-cis-prosten-                                                               oate (Example                                                                 1200)                                                                  1701   ethyl 8-α-methyl-                                                                       8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2-fluoro-17,17-                                         droxy-2-fluoro- dimethyl-8-iso-13-cis-                                        17,17-dimethyl- prostenoic acid                                               8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1200)                                                         1702   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-10a-homo-13-                                            droxy-10a-homo- trans-prostenoic acid                                         13-trans-pros-                                                                tenoate (Example                                                              1201)                                                                  1703   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-10a-homo-8-iso-                                         droxy-10a-homo-8-                                                                             13-trans-prostenoic                                           iso-13-trans-   acid                                                          prostenoate                                                                   (Example 1201)                                                         1704   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-10a-homo-13-cis-                                        droxy-10a-homo- prostenoic acid                                               13-cis-prosten-                                                               oate (Example                                                                 1201)                                                                  1705   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-10a-homo-8-iso-                                         droxy-10a-homo- 13-cis-prostenoic acid                                        8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1201)                                                         1706   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-phenyl-20-meth-                                       droxy-2-phenyl- yl-13-trans-prostenoic                                        20-methyl-13-   acid                                                          trans-prosteno-                                                               ate (Example                                                                  1202)                                                                  1707   ethyl 8α-methyl                                                                         8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-phenyl-20-meth-                                       droxy-2-phenyl- yl-8-iso-13-trans-pros-                                       20-methyl-8-iso-                                                                              tenoic acid                                                   13-trans-pros-                                                                tenoate (Example                                                              1202)                                                                  1708   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-phenyl-20-meth-                                       droxy-2-phenyl- yl-13-cis-prostenoic                                          20-methyl-13-   acid                                                          cis-prostenoate                                                               (Example 1202)                                                         1709   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2-phenyl-20-meth-                                       droxy-2-phenyl- yl-8-iso-13-cis-prosten-                                      20-methyl-8-iso-                                                                              oic acid                                                      13-cis-prosten-                                                               oate (Example                                                                 1202)                                                                  1710   methyl 8β-methyl-                                                                        8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-5-cis,13-trans,17-                                      droxy-6-cis,13- cis-prostatrienoic acid                                       trans,17-cis-                                                                 prostatrienoate                                                               (Example 1203)                                                         1711   methyl 8α-methyl-                                                                       8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  trans,17-cis-prostatri-                                       cis,13-trans,17-                                                                              enoic acid                                                    cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                  1712   methyl 8β-methyl-                                                                        8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-5-cis,13-cis,17-                                        droxy-5-cis,13- cis-prostatrienoic acid                                       cis,17-cis-pros-                                                              tatrienoate                                                                   (Example 1203)                                                         1713   methyl 8α-methyl-                                                                       8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  cis,17-cis-prostatri-                                         cis,13-cis,17-  enoic acid                                                    cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                  1714   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-5-cis,13-trans-                                         droxy-5-cis,13- prostadienoic acid                                            trans-prostadi-                                                               enoate (Example                                                               1204)                                                                  1715   ethyl 8α-methyl-                                                                        8αmethyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  trans-prostadienoic                                           cis,13-trans-   acid                                                          prostadienoate                                                                (Example 1204)                                                         1716   ethyl                                                                         8β-methyl-9-oxo-15-hy-                                                   9-oxo-15-hy-    droxy-5-cis,13-cis-                                           droxy-5-cis,13- prostadienoic acid                                            cis-prostadieno-                                                              ate (Example                                                                  1204)                                                                  1717   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  cis-prostadienoic acid                                        cis,13-cis-pros-                                                              tadienoate (Exam-                                                             ple 204)                                                               1718   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-5-cis,13-                                      droxy-20-ethyl- trans-prostadienoic acid                                      5-cis,13-trans-                                                               prostadienoate                                                                (Example 1205)                                                         1719   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-5-                                       droxy-20-ethyl- cis,13-trans-prostadi-                                        8-iso-5-cis,13- enoic acid                                                    trans-prostadi-                                                               enoate (Example                                                               1205)                                                                  1720   ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-5-cis,13-                                      droxy-2-ethyl-  cis-prostadienoic acid                                        5-cis,13-cis-                                                                 prostadienoate                                                                (Example 1205)                                                         1721   ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-                                         droxy-20-ethyl- 5-cis,13-cis-prosta-                                          8-iso-5-cis,13- dienoic acid                                                  cis-prostadien-                                                               oate (Example                                                                 1205)                                                                  ______________________________________                                        Ex-    Starting alkyl                                                         ample  ester of Example                                                                              Product prostenoic acid                                ______________________________________                                        1722   1210            8β-methyl-9α/β,15-dihy-                                       droxy-16,16-dimethyl-13-                                                      trans-prostenoic acid                                  1723   1211            8α-methyl-9α/β,15-di-                                        hydroxy-16,16-dimethyl-                                                       8-iso-13-trans-pros-                                                          tenoic acid                                            1724   1212            8β-methyl-9α/β,15-dihy-                                       droxy-16,16-dimethyl-13-                                                      cis-prostenoic acid                                    1725   1213            8α-methyl-9α/β,15-dihy-                                      hydroxy-16,16-dimethyl-                                                       8-iso-13-cis-prostenoic                                                       acid                                                   1726   1214            8β-methyl-9α/β,15-dihy-                                       droxy-17,17-dimethyl-                                                         13-trans-prostenoic                                                           acid                                                   1727   1215            8α-methyl-9α/β,15-dihy-                                      droxy-17,17-dimethyl-8-                                                       iso-13-trans-prosten-                                                         oic acid                                               1728   216             8β-methyl-9α/β,15-dihy-                                       droxy-17,17-dimethyl-13-                                                      cis-prostenoic acid                                    1729   1217            8α-methyl-9α/β,15-dihy-                                      droxy-17,17-dimethyl-8-                                                       iso-13-cis-prostenoic                                                         acid                                                   1730   1218            8β-methyl]α/β,15-dihy-                                        droxy-13-trans,17-cis-                                                        prostadienoic acid                                     1731   1219            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-13-trans,17-                                                      cis-prostadienoic acid                                 1732   1220            8β-methyl-9α/β,15-dihy-                                       droxy-13-cis,17-cis-                                                          prostadienoic acid                                     1733   1221            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-13-cis,17-                                                        cis-prostadienoic acid                                 1734   1222            8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-13-trans-                                                      prostenoic acid                                        1735   1223            8α-methyl-9α/β,14-dihy-                                      droxy-20-ethyl-8-iso-                                                         13-trans-prostenoic                                                           acid                                                   1736   1224            8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-13-cis-                                                        prostenoic acid                                        1737   1225            8α-methyl-9α/β,15-dihy-                                      droxy-20-ethul-8-iso-                                  13-cis-prostenoic acid                                                        1738   1230            8β-methyl-9α/β,15-dihy-                                       droxy-7a,7b-bishomo-13-                                                       trans-prostenoic acid                                  1739   1231            8α-methyl-9α/β,15-dihy-                                      droxy-7a,7b-dishomo-8-                                                        iso-13-trans-prosten-                                                         oic acid                                               1740   1232            8β-methyl-9α/β,15-dihy-                                       droxy-7a,7b-bishomo-13-                                                       cis-prostenoic acid                                    1741   1233            8α-methyl-9α/β,15-dihy-                                      droxy-7a,7b-bishomo-8-                                                        iso-13-cis-prostenoic                                                         acid                                                   1742   1234            8β-methyl-9α/β,15-dihy-                                       droxy-2,20-bisethyl-13-                                                       trans-prostenoic acid                                  1743   1235            8α-methyl-9α/β,15-dihy-                                      droxy-2,20-bisethyl-8-                                                        iso-13-trans-prosten-                                                         oic acid                                               1744   1236            8β-methyl-9α/β,15-dihy-                                       droxy-2,20-bisethyl-13-                                                       cis-prostenoic acid                                    1745   1237            8α-methyl-9α/β,15-dihy-                                      droxy-2,20-bisethyl-8-                                                        iso-13-cis-prostenoic                                                         acid                                                   1746   38              8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-16,16-di-                                                         methyl-13-trans-pros-                                                         tenoic acid                                            1747   1239            8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-16,16-di-                                                         methyl-8-iso-13-trans-                                                        prostenoic acid                                        1748   1240            8β-methyl-9α/β,15-diphy-                                      droxy-3-opxa-16,16-di-                                                        metjhyl-13-cis-prosten-                                                       oic acid                                               1749   1241            8α-methyl9α/β,15-dihy-                                       droxy-3-oxa-16,16-di-                                                         methyl-8-iso-13-cis-                                                          prostenoic acid                                        1750   1242            8β-methyl9α/β,15-dihy-                                        droxy-3-oxa-13-trans,17-                                                      cis-prostadienoic acid                                 1751   1243            8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-8-iso-13-                                                         trans,17-cis-prostadi-                                                        enoic acid                                             1752   1244            8β-methyl9α/β,15-dihy-                                        droxy-3-oxa-13-cis,17-                                                        cis-prostadienoic acid                                 1753   1245            8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-8-iso-13-                                                         cis,17-cis-prostadien-                                                        oic acid                                               1754   1246            8β-methyl-9α/β,15-dihy-                                       droxy-7-nor-20-methyl-                                                        13-trans-prostenoic                                                           acid.                                                  1755   1247            8α-methyl-9α/β,15-dihy-                                      droxy-7-nor-20-methyl-                                                        8-iso-13-trans-pros-                                                          tenoic acid                                            1756   1248            8β-methyl-9α/β,15-dihy-                                       droxy-7-nor-20-methyl-                                                        13-cis-prostenoic acid                                 1757   1249            8α-methyl-9α/β,15-dihy-                                      droxy-7-nor-20-methyl-                                                        8-iso-13-cis-prosteno-                                                        ic acid                                                1758   1250            8β-methyl-9α/β,15-dihy-                                       droxy-2-fluoro-17,17-                                                         dimethyl-13-trans-                                                            prostenoic acid                                        1759   1251            8α-methyl-98α/β,15-dihy-                                     droxy-2-fluoro-17,17-                                                         dimethyl-8-iso-13-                                                            trans-prostenoic acid                                  1760   1252            8β-methyl-9α/β,15-dihy-                                       droxy-2-fluoro-17,17-                                                         dimethyl-13-cis-pros-                                                         tenoic acid                                            1761   1253            8α-methyl-9α/β,15-dihy-                                      droxy-2-fluro-17,17-                                                          dimethyl-8-iso-13-cis-                                                        prostenoic acid                                        1762   1254            8β-methyl-9α/β,15-dihy-                                       droxy-10a-homo-13-trans-                                                      prostenoic acid                                        1763   1255            89α-methyl-9α/β,15-dihy-                                     droxy-10a-homo-8-iso-                                                         13-trans-prostenoic                                                           acid                                                   1764   1256            8β-methyl-9α/β,15-dihy-                                       dr5oxy-10a-homo-8-iso-                                                        13-cis-prostenoic acid                                 1766   1258            8β-methyl-9α/β,15-dihy-                                       droxy-2-phenyl-20-meth-                                                       yl-13-trans-prostenoic                                                        acid                                                   1767   1259            8α-methyl-9α/β,15-dihy-                                      droxy-2-phenyl-20-meth-                                                       yl-8-iso-13-trans-pros-                                                       tenoic acid                                            1768   1260            8β-methyl-9α/β,15-dihy-                                       droxy-2-phenyl-20-meth-                                                       yl-13-cis-prostenoic                                                          acid                                                   1769   1261            8α-methyl-9α/β,14-dihy-                                      droxy-32-phenyl-20-meth-                                                      yl-8-iso-13-cis-prosten-                                                      oic acid                                               1770   1262            8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-trans-178-                                                     cis-prostatrienoic acid                                1771   1263            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         trans,17-cis-prostatri-                                                       enoic acid                                             1772   1264            8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-cis,17-                                                        cis-prostatrienoic acid                                1773   1265            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         cis,16-cis-prostatri-                                                         enoic acid                                             1774   1266Z           8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-trans-                                                         prostadienoic acid                                     1775   1267            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         trans-prostadienoic                                                           acid                                                   1776   1268            8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-cis-                                                           prostadienoic acid                                     1777   1269            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         cis-prostadienoic acid                                 1778   1270            8β-methyl-9-α/β,15-dihy-                                      droxy-20-ethyl-5-cis,13-                                                      trans-prostadienoic                                                           acid                                                   1779   1271            8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         5-cis,13-trans-pros-                                                          tadienoic acid                                         1780   1272            8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-5-cis,-                                                        13-cis-prostadienoic                                                          acid                                                   1781   1273            8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-20-iso-                                                        5-cis,13-cis-prosta-                                                          dienoic acid                                           ______________________________________                                    

EXAMPLES 1782-1815

Catalytic hydrogenation of the 13-trans-prostenoic acids or esterslisted below in Table 44 by the procedure described in Example 699furnishes the product prostanoic acids of the table.

                  TABLE 44                                                        ______________________________________                                                Starting 13-                                                                  trans-prostenoic                                                                             Products                                               Ex-     acid or ester of                                                                             8-methylprostanoic                                     ample   Example        acids or esters                                        ______________________________________                                        1782    1206           Methyl 8β-methyl-9α/β,                                        15-dihydroxy- -  prostanoate                           1783    1207           Methyl 8α-methyl-9α/β,                                       15-dihydroxy-8-iso-                                                           prostanoate                                            1784    1210           Ethyl 8β-methyl-9α/β)                                         15-dihydroxy-16,16-                                                           dimethyl-prostanoate                                   1785    1226           Decyl 8β-methyl-9α/β.                                         15-dihydroxy-20-methyl-                                                       prostanoate                                            1786    1655           8β-methyl-9-oxo-15-di-                                                   hydroxy-prostanoic acid                                1787    1656           8α-methyl-(9-oxo-15-di-                                                 hydroxy-8-iso-prostan-                                                        oic acid                                               1788    1659           8β-methyl-9α/β,15-di-                                         hydroxy-prostanoic acid                                1789    1660           8α-methyl-9α/β,15-di-                                        hydroxy-8-iso-prostan-                                                        oic acid                                               1790    1678           8β-methyl-9-oxo-15-hy-                                                   droxy-7a,7b-bishomo-                                                          prostanoic acid                                        1791    1683           8α-methyl-9-oxo-15-                                                     hydroxy-2,20-bisethyl-                                                        8-iso-prostanoic acid                                  1792    1686           8β-methyl-9-oxo-15-                                                      hydroxy-3-oxo-16,16-                                                          dimethyl-prostanoic                                                           acid                                                   1793    1694           8β-methyl-9-oxo-15-                                                      hydroxy-7-nor-20-                                                             methyl-prostanoic acid                                 1794    1702           8β-methyl-9-oxo-15-                                                      hydroxy-10a-homo-                                                             prostanoic acid                                        1795    1523           8β-methyl-9α/β,11α,15-                                  trihydroxy-prostanoic                                                         acid                                                   1796    1524           8α-methyl-9α/β,11α,15-                                 trihydroxy-8-iso-                                                             prostanoic acid                                        1797    1527           8β-methyl-9α/β,11α,15-                                  trihydroxy-16,16-di-                                                          methyl-prostanoic acid                                 1798    1531           8β-methyl-9α/β,11α,15-                                  trihydroxy-17,17-di-                                                          methyl-prostanoic acid                                 1799    1539           8β-methyl-9α/β-11α,15-                                  trihydroxy-20-ethyl-                                                          prostanoic acid                                        1800    1552           8α-methyl-9α/β,11α,15-                                 trihydroxy-7a,7b-bis-                                                         homo-8-iso-prostanoic                                                         acid                                                   1801    1551           8β-methyl-9α/β,11α,15-                                  trihydroxy-7a,7b-bis-                                                         homo-prostanoic acid                                   1802    1555           8β-methyl-9α/β,11α,15-                                  trihydroxy-2-ethyl-                                                           prostanoic acid                                        1803    1559           8β-methyl-9α/β,11α,15-                                  trihydroxy-3,3,20-tri-                                                        methyl-prostanoic acid                                 1804    1563           8β-methyl-9α/β,11α,15-                                  trihydroxy-3-oxa-                                                             prostanoic acid                                        1805    1567           8β-methyl-9α/β,11α,15-                                  trihydroxy-3-oxa-13-                                                          16-dimethyl-prostanoic                                                        acid                                                   1806    1587           8β-methyl-9α/β,11α,15-                                  trihydroxy-7a-homo-                                                           16,16-dimethyl-pro-                                                           stanoic acid                                           1807    1643           Ethyl 8β-methyl-9α/β,                                         11α,15-trihydroxy-3-                                                    oxa-17,17-dimethyl-                                                           prostanoic acid                                        1808    1816           8β,15-dimethyl-9α/β,15-                                       dihydroxy-prostanoic -  acid                           1809    1817           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-prostanoic                                                         acid                                                   1810    1819           8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-                                                             prostanoic acid                                        1811    1834           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-                                                      prostanoic acid                                        1812    1835           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-                                                       prostanoic acid                                        1813    1837           8α,15-dimethyl-9-oxo-                                                   11α,15-dihydroxy-8-                                                     iso-prostanoic acid                                    1814    1843           8β,15-dimethyl-9-oxo- -  11α,15-dihydrox                           y-7a,                                                                         7b-bishomo-prostanoic                                                         acid                                                   1815    1849           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-                                                     oxa-prostanoic acid                                    ______________________________________                                    

EXAMPLES 1816-1859

Treatment by the procedure described in Example 1082 of the8-methyl-9α/β,15-dihydroxy-prostenoic acids listed in Table 45 belowsuccessively with 2,3-dichloro-5,6-dicyanobenzoquinone to give thecorresponding 15-keto derivatives; 2.4 equivalents each of triethylamineand trimethylsilyl chloride to give the corresponding 9α/β-0--trimethylsilyl ether trimethylsilyl prostenoate ester in the instanceof the 11α-hydroxy derivatives an additional 1.1 equivalent each oftriethylamine and trimethylsilyl chloride is used and the11α-0-trimethylsilyl ether derivative is obtained); methyl magnesiumbromide to give the 15-methyl-15-hydroxy bis or tris trimethylsilylblocked ether-ester; methanol-water-acetic acid for deblocking of thetrimethylsilyl ether and ester blocking groups to give the listed9α/β-hydroxy-15-methyl-15-hydroxy derivatives. In the 11- -deoxy seriestreatment of these 9α/-62 -hydroxy-15-methyl-15-hydroxy products withCollins reagent in methylene chloride provides the corresponding11-deoxy-9-oxo-15 -hydroxy-15- methyl-prostenoic acids, also listed inthe table. In the 11α-hydroxy series, treatment of the 9α/β,11α-15-trihydroxy-15 -methyl derivatives with 1.1 molar equivalents eachof triethylamine and trimethylsilyl chloride provides the corresponding11α-0-trimethylsilyloxy-9α/β,15-dihydroxy derivative, which on oxidationin the usual way with Collins reagent in methylene chloride followed bysilyl ether cleavage (treatment with methanol-water-acetic acid by theprocedure described in Example 1082 ) provides the corresponding9-ozo-11α,15-dihydroxy-15-methyl-prostenoic acids of the Table.

                  TABLE 45                                                        ______________________________________                                                Starting 9α/β, (or                                                 9α),15-dihydroxy-                                                       or 9α/β(or 9α),                                                             Product                                                        11α,15-dihydroxy                                                                       8,15-dimethyl-15-hy-                                   Ex-     derivative of  droxy-prostanoic                                       ample   Example        acids                                                  ______________________________________                                        1816    1659           8β,15-dimethyl-9α,β,15-                                       dihydroxy-13-trans-                                                           prostenoic acid                                        1817    1659           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-13-trans-                                                          prostenoic acid                                        1818    1660           8α,15-dimethyl-9α,15-                                             dihydroxy-8-iso-13-                                                           trans-prostenoic acid                                  1819    1660           8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-13-                                                          trans-prostenoic acid                                  1820    1730           8β,15-dimethyl-9α/β,15-                                       dihydroxy-13-trans,17-                                                        cis-prostadienoic acid                                 1821    1730           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-13-trans-                                                          17-cis-prostadienoic                                                          acid                                                   1822    1731           8α,15-dimethyl-9α/β,15-                                      dihydroxy-8-iso-13-                                                           trans,17-cis-prosta-                                                          dienoic acid                                           1823    1731           8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-13- -  trans,17-cis-prosta-                                  dienoic acid                                           1824    1738           8β,15-dimethyl-9α/β,                                          15-dihydroxy-7a,7b-                                                           bishomo-13-trans-                                                             prostenoic acid                                        1825    1738           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-7a,7b-bis-                                                         homo-13-trans-prost-                                                          enoic acid                                             1826    1746           8β,15-dimethyl-9α/β                                           15-dihydroxy-3-oxa-16,                                                        16-dimethyl-13-trans-                                                         prostenoic acid                                        1827    1746           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-16,                                                          16-dimethyl-13-trans-                                                         prostenoic acid                                        1828    1750           8β,15-dimethyl-9α/β,                                          15-dihydroxy-3-oxa-                                                           13-trans,17-cis-                                                              prostadienoic acid                                     1829    1750           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                           1830    1770           8β,15-dimethyl-9α/β,                                          15-dihydroxy-5-cis,                                                           13-trans,17-cis-prosta-                                                       trienoic acid                                          1831    1770           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                          1832    1778           8β,15-dimethyl-9α/β,                                          15-dihydroxy-20-ethyl-                                                        5-cis,13-trans-                                                               prostadienoic acid                                     1833    1778           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-20-ethyl-5-                                                        cis,13-trans-prosta-                                                          dienoic acid                                           1834    1523           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-13-                                                   trans-prostenoic acid                                  1835    1523           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-13-                                                    trans-prostenoic acid                                  1836    1524           8α,15-dimethyl-9α/β,                                         11α,15-trihydroxy-8-                                                    iso-13-trans-pros-                                                            tenoic acid                                            1837    1524           8α,15-dimethyl-9-oxo-                                                   11α,15-dihydroxy-                                                       8-iso-13-trans-                                                               prostenoic acid                                        1838    1535           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-13-                                                   trans,17-cis-prosta-                                                          dienoic acid                                           1839    1535           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-13-                                                    trans,17-cis-prosta-                                                          dienoic acid                                           1840    1539           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-20-                                                   ethyl-13-trans-pro-                                                           stenoic acid                                           1841    1539           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-20-                                                    ethyl-13-trans-pro-                                                           stenoic acid                                           1842    1551           8α,15-dimethyl-9α/β,                                         11α,15-trihydroxy-7a,                                                   7b-bishomo-13-trans-                                                          prostenoic acid                                        1843    1551           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-7a,                                                    7b-bishomo-13-trans-                                                          prostenoic acid                                        1844    1555           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-2-                                                    ethyl-13-trans-                                                               prostenoic acid                                        1845    1555           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-2-                                                     ethyl-13-trans-                                                               prostenoic acid                                        1846    1559           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3,3                                                   20-trimethyl-13-trans-                                                        prostenoic acid                                        1847    1559           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3,3,                                                   20-trimethyl-13-trans-                                                        prostenoic acid                                        1848    1563           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3-                                                    oxa-13-trans-prostenoic                                                       acid                                                   1849    1563           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-                                                     oxa-13-trans-prostenoic                                                       acid                                                   1850    1571           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3-                                                    oxa-13-trans,17-cis-                                                          prostadienoic acid                                     1851    1571           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-oxa.                                                 13-trans,17-cis-prosta-                                                       dienoic acid                                           1852    1599           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-5-                                                    cis,13-trans-prosta-                                                          dienoic acid                                           1853    1599           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-5-                                                     cis,13-trans-prosta-                                                          dienoic acid                                           1854    1603           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-5-cis,                                                13-trans,17-cis-prosta-                                                       trienoic acid                                          1855    1603           8α,15-dimethyl-9-oxo-                                                   11α,15-dihydroxy-5-                                                     cis,13-trans,17-cis-                                                          prostatrienoic acid                                    1856    1611           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-4-nor-                                                20-methyl-5-cis,13-                                                           trans-prostadienoic                                                           acid                                                   1857    1611           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-4-                                                     nor-20-methyl-5-cis,                                                          13-trans-prostadienoic                                                        acid                                                   1858    1623           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-4a,                                                   4b-bishomo-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                          1859    1623           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-4a,                                                    4b-bishomo-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                          ______________________________________                                    

EXAMPLES 1860-1876

Treatment of the 8,15-dimethyl-9-oxo-11α-hydroxy derivatives listed inTable 46 below with equeous acetic acid by the procedure described inExample 1387 is productive of the corresponding 10 -prostenoic acidproducts of the table.

                  TABLE 46                                                        ______________________________________                                              Starting 8,15-di-                                                             methyl-9-oxo-11α-                                                                       Product                                                 Ex-   hydroxy deriva- 8,15-dimethyl-9-oxo-                                    ample tives of Example                                                                              10-prostenoic acid                                      ______________________________________                                        1860  1835            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-10,13-trans-                                                       prostadienoic acid                                      1861  1837            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-10,                                                          13-trans-prostadienoic                                                        acid                                                    1862  1839            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-10,13-trans,                                                       17-cis-prostatrienoic                                                         acid                                                    1863  1841            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-20-ethyl-                                                          10,13-trans-prosta-                                                           dienoic acid                                            1864  1843            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-7a,7b-bis-                                                         homo-10,13-trans-                                                             prostadienoic acid                                      1865  1845            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-2-ethyl-10,13-                                                        trans-prostadienoic                                                           acid                                                    1866  1847            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3,3,20-tri-                                                        methyl-10,13-trans-                                                           prostadienoic acid                                      1867  1849            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-10,13-                                                       trans-prostadienoic                                                           acid                                                    1868  1851            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-10,                                                          13-trans,17-cis-prosta                                                        trienoic acid                                           1869  1853            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,10,13-                                                       trans-prostatrienoic                                                          acid                                                    1870  1855            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,10,                                                          13-trans,17-cis-prosta-                                                       tetraenoic acid                                         1871  1857            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-4-nor-20-                                                          methyl-5-cis,10,13-                                                           trans-prostatrienoic                                                          acid                                                    1872  1859            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-4a,4b-bis-                                                         homo-5-cis,10,13-trans,                                                       17-cis-prostatetraenoic                                                       acid                                                    1873  1812            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-10-prostenoic                                                         acid                                                    1874  1815            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-3-oxa-10-                                                             prostenoic acid                                         1875  1814            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-7a,7b-bishomo-                                                        10-prostenoic acid                                      1876  1813            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-10-                                                          prostenoic acid                                         ______________________________________                                    

EXAMPLE 1877 Preparation of 3-methoxy-1-octyne

To an ice-cooled solution of 63 g. of 1-octyn-3-ol in 300 ml. ofdimethoxyethane is added under an inert atmosphere 312 ml. of 1.6 Mn-butyllithium in hexane dropwise over 1 hour. To the mixture is thenadded 145 g. of methyl iodide and the resulting mixture is stirred atambient temperatures for 24 hours and then heated to 60° C. for 1 hour.The mixture is cooled and poured into cold dilute hydrochloric acid. Theorganic phase is separated, washed with water and saturated brine, dried(Na₂ SO₄), and evaporated to an oil, dried (Na₂ SO₄), and evaporated toan oil. Fractional distillation of the oil in vacuo yields the productas a colorless oil.

EXAMPLE 1878 Preparation of 1-Iodo-3-methoxy-trans-1-octene

Treatment of 3-methoxy-1-octyne (Example 1877) with disiamylborane,trimethylamine oxide, sodium hydroxide and iodine by the proceduredescribed in Example 996 furnishes the title product.

EXAMPLE 1879 Preparation of 3-Methoxy-trans-1-octenyl lithium

Treatment of 1-iodo-3-methoxy-trans-1-octane (Example 1878) with butyllithium in the manner of Example 931 pro provides a toluene-hexanesolution of the subject trans-vinyl lithium derivative.

EXAMPLE 1880 Preparation of Lithium(3-methoxy-trans-1-octenyl)trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to themethod of Example 905 from a hydrocarbon solution of3-methoxy-trans-1-oxtanyl lithium (Example 1879) and trimethylaluminum.

EXAMPLES 1881-1895

Treatment of the cycloslkenones listed in Table 47 withlithium(3-methoxy-trans-1-octenyl) trimethylalanate (Example 1880) bythe procedure described in Example 957 with the omission of the 80%aqueous acetic acid treatment (80° C., 1 hour) followed by saponficationof the intermediate alkyl prostenoates by the procedure described inExample 122 furnishes the product 9 -oxo-15-methoxy-13-trans-prostenoicacids of the table.

                  TABLE 47                                                        ______________________________________                                                Starting cyclo-                                                                              Product 9-oxo-15-                                      Ex-     alkenone of    methoxy-13-trans -ample Example prostenoic             ______________________________________                                                               acid                                                   1881    23             9-oxo-7a,7b-bishomo-                                                          15-methoxy-13-trans-                                                          prostenic acid                                         1882    31             9-oxo-2-ethyl-15-                                                             methoxy-13-trans-pro-                                                         stenoic acid                                           1883    41             9-oxo-3,3-dimethyl-                                                           15-methoxy-13-trans-                                                          prostenoic acid                                        1884    46             9-oxo-3-oxa-15-methoxy-                                                       13-trans-prostenoic                                                           acid                                                   1885    53             9-oxo-7-nor-15-methoxy-                                                       13-trans-prostenoic                                                           acid                                                   1886    70             9-oxo-2-fluoro-15-                                                            methoxy-13-trans-                                                             prostenoic acid                                        1887    74             9-oxo-7a-homo-15-                                                             methoxy-13-trans-pro-                                                         stenoic acid                                           1888    79             9-oxo-2-phenyl-15-                                                            methoxy-13-trans-pro-                                                         steoic acid                                            1889    99             9-oxo-2-methyl-15-                                                            methoxy-13-trans-pro-                                                         stenoic acid                                           1890    111            9-oxo-10a-homo-15-                                                            methoxy-13-trans-                                                             prostenoic acid                                        1891    118            9-oxo-3-thia-15-                                                              methoxy-13-trans-                                                             prostenoic acid                                        1892    900            9-oxo-15-methoxy-3-                                                           cis,13-trans-pro-                                                             stadienoic acid                                        1893    1144           9-oxo-4-nor-15-methoxy-                                                       13-trans-prostadienoic                                                        acid                                                   1894    1145           9-oxo-4-homo-15-                                                              methoxy-5-cis,13-                                                             trans-prostedienoic                                                           acid                                                   1895    1146           9-oxo-4a,4b-bishomo-                                                          15-methoxy-13-trans-                                                          prostadienoic acid                                     ______________________________________                                    

EXAMPLE 1896-1910

Treatment of the 9-oxo-15-methoxy-13-trans-prostenoic acids listed inTable 48 below with lithium perhydro-9β-boraphenalylhydride by theprocedure described in Example 737 furnishes the9α-hydroxy-15-methoxy-13-trans-prostenoic acids of the Table.

                  TABLE 48                                                        ______________________________________                                              Starting 9-oxo-                                                               15-methoxy-13-                                                                trans-prosten- Product 9α-hydroxy-15-                             Ex-   oic acid of    methoxy-13-trans-                                        ample Example        prostenoic acid                                          ______________________________________                                        1896  1881           9α-hydroxy-7a,7b-bis-                                                   homo-15-methoxy-13-                                                           trans-prostenoic acid                                    1897  1882           9α-hydroxy-2-ethyl-                                                     15-methoxy-13-trans-                                                          prostenoic acid                                          1898  1883           9α-hydroxy-3,3-dimethyl-                                                15-methoxy-13-trans-                                                          prostenoic acid                                          1899  1884           9α-hydroxy-3-oxa-15-                                                    methoxy-13-trans-                                                             prostenoic acid                                          1900  1885           9α-hydroxy-7-nor-15-                                                    methoxy-13-trans-pro- -  prostenoic acid                 1901  1886           9α-hydroxy-2-fluoro-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                          1902  1887           9α-hydroxy-7a-homo-                                                     15-methoxy-13-trans-                                                          prostenoic acid                                          1903  1888           9α-hydroxy-2-phenyl-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                          1904  1889           9α-hydroxy-2-methyl-                                                    methoxy-13-trans-                                                             prostenoic acid                                          1905  1890           9α-hydroxy-10a-homo-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                          1906  1891           9α-hydroxy-3-thia-15-                                                   methoxy-13-trans-                                                             prostenoic acid                                          1907  1892           9α-hydroxy-15-methoxy-                                                  5-cis,13-trans-prosta-                                                        dienoic acid                                             1908  1893           9α-hydroxy-4-nor-15-                                                    methoxy-5-cis,13-                                                             trans-prostadienoic                                                           acid                                                     1909  1894           9α-hydroxy-4-homo-15-                                                   methoxy-5-cis,13-trans-                                                       prostadienoic acid                                       1910  1895β     9α-hydroxy-4a,4b-bis-                                                   homo-15-methoxy-13- -  trans-prostenoic                  ______________________________________                                                             acid                                                 

EXAMPLE 1911 Preparation of2-(6-carboxy-2-cia-hexenyl)-3,4-oxidocyclopentanol

A solution of 5.0 g. (35 mmoles) of5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactol (isomeric mixture;E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 311) in 25 ml. ofDMSO is added during 0.5 minutes at 20° C. to a stirred solution of theWithig reagent [E. J. Corey et al., JACS, 91 5675 (1969); also Example1108] and dimayl sodium prepared from 23.5 g. (53 mmoles) of4-carboxybutyltriphenyl phosphonium bromide, 6.1 g. (140 mmoles) of 57%sodium hydride dispersion, and 230 ml. of DMSO (dimethylsulfoxide).

The solution is stirred at ambient temperatures for 2 hours and pouredinto a stirred mixture of methylene chloride, ice, and hydrochloricacid. The reaction mixture is worked up as described in Example 1105,andthe crude product is purified by dry column chromatography on silicagel to provide the title compound (mixture of two stereoisomers) as anoil, IR (film) 3450, 1710, and 832 cm⁻¹.

EXAMPLE 1912 Preparation of2-(6-carboxy-2-cis-hexanyl)-3,4-oxidocyclopentanene

A stirred solution of 2.98 g. (13.2 mmoles) of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentenol (Example 1911) in 66ml. of acetone is treated dropwise with 3.30 ml. of 8M chromic acid in8M M₂ SO₄ during 20 minutes at -10° to -5° C. The solution is stirred at-5° C. for 10 minutes and treated successively with a few drops ofisopropenol and 12 ml. of water. The mixture is filtered, and thefiltrate is concentrated saturated with sodium chloride, and extractedwith ethyl acetate. The extract is washed with brine, dried over MgSO₄,and evaporated to give an oil, XR (film) 1740, 1710, and 840 cm⁻².

EXAMPLE 1913 Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of (pH or 10.2-10.5) of 2.42 g. (10.8 mmoles) of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentenene (Example 1912) 4.58g. (43.2 mmoles) of sodium carbonate, and 216 ml. of water is allowed tostand at room temperature under nitrogen for 24 hours. The solution isacidified at 15° C. with hydrochloric acid and extracted with ethylacetate. The extract is washed with brine, dried over MgSO₄, andevaporated to give an oil; IR (film) 1700 (carbonyl groups) and 1630cm⁻² (conjugated olefin); MDR 7.11 (1), 5.54 (2), and 4.95 (1)δ.

We claim:
 1. Compounds of the formula: ##STR35## wherein p is an integerfrom 3 to 6 inclusive.
 2. The compound according to claim 1 wherein p is3; 2-(6-carboxy-2-cis-hexenyl)-3-hydroxycyclopent-4-en-1-one.